Mechanomedicine

Posted on
mechanomedicine
Mechanomedicine

References

  1. Fung, Y.-c. Biomechanics: Mechanical Properties of Living Tissues (Springer Science & Business Media, 2013).

  2. Chien, S., Engler, A. J. & Wang, P. Y. Molecular and Cellular Mechanobiology (Springer, 2016).

  3. Ingber, D. Mechanobiology and diseases of mechanotransduction. Ann. Med. 35, 564–577 (2003).

    Article  Google Scholar 

  4. Iskratsch, T., Wolfenson, H. & Sheetz, M. P. Appreciating force and shape — the rise of mechanotransduction in cell biology. Nat. Rev. Mol. Cell Biol. 15, 825–833 (2014).

    Article  Google Scholar 

  5. Yoon, H. et al. Decoding tissue biomechanics using conformable electronic devices. Nat. Rev. Mater. 10, 4–27 (2025).

    Article  Google Scholar 

  6. Kwon, K. et al. A battery-less wireless implant for the continuous monitoring of vascular pressure, flow rate and temperature. Nat. Biomed. Eng. 7, 1215–1228 (2023). This article reports an implantable sensor for wireless monitoring of vascular biomechanics such as pressure and flow rate.

    Article  Google Scholar 

  7. Mitragotri, S. Healing sound: the use of ultrasound in drug delivery and other therapeutic applications. Nat. Rev. Drug Discov. 4, 255–260 (2005).

    Article  Google Scholar 

  8. Vogel, V. & Sheetz, M. Local force and geometry sensing regulate cell functions. Nat. Rev. Mol. Cell Biol. 7, 265–275 (2006).

    Article  Google Scholar 

  9. Discher, D. E., Mooney, D. J. & Zandstra, P. W. Growth factors, matrices, and forces combine and control stem cells. Science 324, 1673–1677 (2009).

    Article  Google Scholar 

  10. Zhang, X. et al. Unraveling the mechanobiology of immune cells. Curr. Opin. Biotechnol. 66, 236–245 (2020).

    Article  Google Scholar 

  11. Zhang, Y., Yu, J., Bomba, H. N., Zhu, Y. & Gu, Z. Mechanical force-triggered drug delivery. Chem. Rev. 116, 12536–12563 (2016).

    Article  Google Scholar 

  12. Davis, M. J., Earley, S., Li, Y.-S. & Chien, S. Vascular mechanotransduction. Physiological Rev. 103, 1247–1421 (2023).

    Article  Google Scholar 

  13. Carter, D. R., Beaupré, G. S., Giori, N. J. & Helms, J. A. Mechanobiology of skeletal regeneration. Clin. Orthop. Relat. Res. 355, S41–S55 (1998).

    Article  Google Scholar 

  14. Huxley, H. & Hanson, J. Changes in the cross-striations of muscle during contraction and stretch and their structural interpretation. Nature 173, 973–976 (1954).

    Article  Google Scholar 

  15. Humphrey, J. D., Dufresne, E. R. & Schwartz, M. A. Mechanotransduction and extracellular matrix homeostasis. Nat. Rev. Mol. Cell Biol. 15, 802–812 (2014).

    Article  Google Scholar 

  16. Martins, R. P., Finan, J. D., Farshid, G. & Lee, D. A. Mechanical regulation of nuclear structure and function. Annu. Rev. Biomed. Eng. 14, 431–455 (2012).

    Article  Google Scholar 

  17. Shin, Y. & Brangwynne, C. P. Liquid phase condensation in cell physiology and disease. Science 357, eaaf4382 (2017).

    Article  Google Scholar 

  18. Krammer, A., Lu, H., Isralewitz, B., Schulten, K. & Vogel, V. Forced unfolding of the fibronectin type III module reveals a tensile molecular recognition switch. Proc. Natl. Acad. Sci. USA 96, 1351–1356 (1999). This article reports that mechanical stretching of fibronectin straightens the RGD-loop, thus acting as mechano-chemical switch by decreasing integrin affinity.

    Article  Google Scholar 

  19. Rief, M., Gautel, M., Oesterhelt, F., Fernandez, J. M. & Gaub, H. E. Reversible unfolding of individual titin immunoglobulin domains by AFM. Science 276, 1109–1112 (1997).

    Article  Google Scholar 

  20. Nia, H. T., Munn, L. L. & Jain, R. K. Physical traits of cancer. Science 370, eaaz0868 (2020).

    Article  Google Scholar 

  21. Hickler, R. B. Aortic and large artery stiffness: current methodology and clinical correlations. Clin. Cardiol. 13, 317–322 (1990).

    Article  Google Scholar 

  22. Bonnans, C., Chou, J. & Werb, Z. Remodelling the extracellular matrix in development and disease. Nat. Rev. Mol. Cell Biol. 15, 786–801 (2014).

    Article  Google Scholar 

  23. Younesi, F. S., Miller, A. E., Barker, T. H., Rossi, F. M. V. & Hinz, B. Fibroblast and myofibroblast activation in normal tissue repair and fibrosis. Nat. Rev. Mol. Cell Biol. 25, 617–638 (2024).

    Article  Google Scholar 

  24. Chaudhuri, O., Cooper-White, J., Janmey, P. A., Mooney, D. J. & Shenoy, V. B. Effects of extracellular matrix viscoelasticity on cellular behaviour. Nature 584, 535–546 (2020).

    Article  Google Scholar 

  25. Vogel, V. Unraveling the mechanobiology of extracellular matrix. Annu. Rev. Physiol. 80, 353–387 (2018).

    Article  Google Scholar 

  26. Sack, I. Magnetic resonance elastography from fundamental soft-tissue mechanics to diagnostic imaging. Nat. Rev. Phys. 5, 25–42 (2023).

    Article  Google Scholar 

  27. Zhou, S. et al. Clinical validation of a wearable ultrasound sensor of blood pressure. Nat. Biomed. Eng. 9, 865–881 (2025).

    Article  Google Scholar 

  28. He, Y. et al. Medical image-based computational fluid dynamics and fluid-structure interaction analysis in vascular diseases. Front. Bioeng. Biotechnol. 10, 855791 (2022).

    Article  Google Scholar 

  29. Massey, A. et al. Mechanical properties of human tumour tissues and their implications for cancer development. Nat. Rev. Phys. 6, 269–282 (2024).

    Article  Google Scholar 

  30. Sigrist, R. M. S., Liau, J., Kaffas, A. E., Chammas, M. C. & Willmann, J. K. Ultrasound elastography: review of techniques and clinical applications. Theranostics 7, 1303–1329 (2017).

    Article  Google Scholar 

  31. Ku, D. N. Blood flow in arteries. Annu. Rev. Fluid Mech. 29, 399–434 (1997).

    Article  MathSciNet  Google Scholar 

  32. Song, E., Li, J., Won, S. M., Bai, W. & Rogers, J. A. Materials for flexible bioelectronic systems as chronic neural interfaces. Nat. Mater. 19, 590–603 (2020).

    Article  Google Scholar 

  33. Chen, G. et al. Electronic textiles for wearable point-of-care systems. Chem. Rev. 122, 3259–3291 (2022).

    Article  Google Scholar 

  34. Patel, N., Chong, K. & Baydur, A. Methods and applications in respiratory physiology: respiratory mechanics, drive and muscle function in neuromuscular and chest wall disorders. Front. Physiol. 13, 838414 (2022).

    Article  Google Scholar 

  35. Viljoen, A. et al. Force spectroscopy of single cells using atomic force microscopy. Nat. Rev. Methods Primers 1, 63 (2021).

    Article  Google Scholar 

  36. Sung, K.-L., Sung, L. A., Crimmins, M., Burakoff, S. J. & Chien, S. Determination of junction avidity of cytolytic T cell and target cell. Science 234, 1405–1408 (1986).

    Article  Google Scholar 

  37. Urbanska, M. et al. A comparison of microfluidic methods for high-throughput cell deformability measurements. Nat. Methods 17, 587–593 (2020).

    Article  Google Scholar 

  38. Nyberg, K. D. et al. The physical origins of transit time measurements for rapid, single cell mechanotyping. Lab Chip 16, 3330–3339 (2016).

    Article  Google Scholar 

  39. Usami, S., Chen, H. H., Zhao, Y., Chien, S. & Skalak, R. Design and construction of a linear shear stress flow chamber. Ann. Biomed. Eng. 21, 77–83 (1993).

    Article  Google Scholar 

  40. Dembo, M. & Wang, Y.-L. Stresses at the cell-to-substrate interface during locomotion of fibroblasts. Biophys. J. 76, 2307–2316 (1999).

    Article  Google Scholar 

  41. Legant, W. R. et al. Measurement of mechanical tractions exerted by cells in three-dimensional matrices. Nat. Methods 7, 969–971 (2010).

    Article  Google Scholar 

  42. Bustamante, C. J., Chemla, Y. R., Liu, S. & Wang, M. D. Optical tweezers in single-molecule biophysics. Nat. Rev. Methods Primers 1, 25 (2021).

    Article  Google Scholar 

  43. Marshall, B. T. et al. Direct observation of catch bonds involving cell-adhesion molecules. Nature 423, 190–193 (2003).

    Article  Google Scholar 

  44. Thomas, W. E., Trintchina, E., Forero, M., Vogel, V. & Sokurenko, E. V. Bacterial adhesion to target cells enhanced by shear force. Cell 109, 913–923 (2002).

    Article  Google Scholar 

  45. Ma, R. et al. Molecular mechanocytometry using tension-activated cell tagging. Nat. Methods 20, 1666–1671 (2023). This article reports a high-throughput platform for mechanophenotyping at the molecular level by integrating a DNA-based force sensor and flow cytometry.

    Article  Google Scholar 

  46. Grashoff, C. et al. Measuring mechanical tension across vinculin reveals regulation of focal adhesion dynamics. Nature 466, 263–266 (2010).

    Article  Google Scholar 

  47. Sader, J. E., Gomez, A., Neumann, A. P., Nunn, A. & Roukes, M. L. Data-driven fingerprint nanoelectromechanical mass spectrometry. Nat. Commun. 15, 8800 (2024).

    Article  Google Scholar 

  48. Sage, E. et al. Single-particle mass spectrometry with arrays of frequency-addressed nanomechanical resonators. Nat. Commun. 9, 3283 (2018).

    Article  Google Scholar 

  49. Gimbrone, M. A. & García-Cardeña, G. Endothelial cell dysfunction and the pathobiology of atherosclerosis. Circ. Res. 118, 620–636 (2016).

    Article  Google Scholar 

  50. Nerem, R. M. Vascular fluid mechanics, the arterial wall, and atherosclerosis. J. Biomech. Eng. 114, 274–282 (1992).

    Article  Google Scholar 

  51. Wang, D., Brady, T., Santhanam, L. & Gerecht, S. The extracellular matrix mechanics in the vasculature. Nat. Cardiovascular Res. 2, 718–732 (2023).

    Article  Google Scholar 

  52. Turjman, A. S., Turjman, F. & Edelman, E. R. Role of fluid dynamics and inflammation in intracranial aneurysm formation. Circulation 129, 373–382 (2014).

    Article  Google Scholar 

  53. Niklason, L. E. & Lawson, J. H. Bioengineered human blood vessels. Science 370, eaaw8682 (2020).

    Article  Google Scholar 

  54. Juhl, O. J. et al. Update on the effects of microgravity on the musculoskeletal system. NPJ Microgravity 7, 28 (2021).

    Article  Google Scholar 

  55. Ozcivici, E. et al. Mechanical signals as anabolic agents in bone. Nat. Rev. Rheumatol. 6, 50–59 (2010).

    Article  Google Scholar 

  56. Goldring, S. R. & Goldring, M. B. Changes in the osteochondral unit during osteoarthritis: structure, function and cartilage–bone crosstalk. Nat. Rev. Rheumatol. 12, 632–644 (2016).

    Article  Google Scholar 

  57. Heinegård, D. & Saxne, T. The role of the cartilage matrix in osteoarthritis. Nat. Rev. Rheumatol. 7, 50–56 (2011).

    Article  Google Scholar 

  58. Mow, V. C. & Guo, X. E. Mechano-electrochemical properties of articular cartilage: their inhomogeneities and anisotropies. Annu. Rev. Biomed. Eng. 4, 175–209 (2002).

    Article  Google Scholar 

  59. Pillai, E. K. & Franze, K. Mechanics in the nervous system: From development to disease. Neuron 112, 342–361 (2024).

    Article  Google Scholar 

  60. Kruse, S. A. et al. Magnetic resonance elastography of the brain. Neuroimage 39, 231–237 (2008).

    Article  Google Scholar 

  61. Hain, E. G. et al. Dopaminergic neurodegeneration in the mouse is associated with decrease of viscoelasticity of substantia nigra tissue. PLoS One 11, e0161179 (2016).

    Article  Google Scholar 

  62. Miéville, A. & Vogel, V. Cell niche properties as tuned by physical factors: ECM proteins as mechanochemical switches. Curr. Opin. Biomed. Eng. 35, 100600 (2025).

    Article  Google Scholar 

  63. Levental, K. R. et al. Matrix crosslinking forces tumor progression by enhancing integrin signaling. Cell 139, 891–906 (2009).

    Article  Google Scholar 

  64. Arnoldini, S. et al. Novel peptide probes to assess the tensional state of fibronectin fibers in cancer. Nat. Commun. 8, 1793 (2017).

    Article  Google Scholar 

  65. Agrawal, A. et al. Mechanical signatures in cancer metastasis. NPJ Biol. Phys. Mech. 2, 3 (2025).

    Article  Google Scholar 

  66. McQuitty, C. E., Williams, R., Chokshi, S. & Urbani, L. Immunomodulatory role of the extracellular matrix within the liver disease microenvironment. Front. Immunol. 11, 574276 (2020).

    Article  Google Scholar 

  67. Yang, B. et al. Stopping transformed cancer cell growth by rigidity sensing. Nat. Mater. 19, 239–250 (2020).

    Article  Google Scholar 

  68. Guimarães, C. F., Gasperini, L., Marques, A. P. & Reis, R. L. The stiffness of living tissues and its implications for tissue engineering. Nat. Rev. Mater. 5, 351–370 (2020).

    Article  Google Scholar 

  69. Dagdeviren, C. et al. Conformal piezoelectric systems for clinical and experimental characterization of soft tissue biomechanics. Nat. Mater. 14, 728–736 (2015).

    Article  Google Scholar 

  70. Sim, K. et al. An epicardial bioelectronic patch made from soft rubbery materials and capable of spatiotemporal mapping of electrophysiological activity. Nat. Electron. 3, 775–784 (2020).

    Article  Google Scholar 

  71. Kim, J.-H. et al. A conformable sensory face mask for decoding biological and environmental signals. Nat. Electron. 5, 794–807 (2022).

    Article  Google Scholar 

  72. Kim, J. et al. A soft and transparent contact lens for the wireless quantitative monitoring of intraocular pressure. Nat. Biomed. Eng. 5, 772–782 (2021).

    Article  Google Scholar 

  73. Hou, B., Yang, D., Ren, X., Yi, L. & Liu, X. A tactile oral pad based on carbon nanotubes for multimodal haptic interaction. Nat. Electron. 7, 777–787 (2024).

    Article  Google Scholar 

  74. Hu, H. et al. Stretchable ultrasonic arrays for the three-dimensional mapping of the modulus of deep tissue. Nat. Biomed. Eng. 7, 1321–1334 (2023). This article reports stretchable ultrasonic arrays for measuring deep-tissue modulus, validated in the human body.

    Article  Google Scholar 

  75. Kennedy, B. F., Wijesinghe, P. & Sampson, D. D. The emergence of optical elastography in biomedicine. Nat. Photonics 11, 215–221 (2017).

    Article  Google Scholar 

  76. Zaitsev, V. Y. et al. Strain and elasticity imaging in compression optical coherence elastography: the two-decade perspective and recent advances. J. Biophotonics 14, e202000257 (2021).

    Article  Google Scholar 

  77. Singh, M., Hepburn, M. S., Kennedy, B. F. & Larin, K. V. Optical coherence elastography. Nat. Rev. Methods Primers 5, 39 (2025).

    Article  Google Scholar 

  78. Kirby, M. A. et al. Optical coherence elastography in ophthalmology. J. Biomed. Opt. 22, 1–28 (2017).

    Article  Google Scholar 

  79. Campos, L. D., Santos Junior, V. A., Pimentel, J. D., Carregã, G. L. F. & Cazarin, C. B. B. Collagen supplementation in skin and orthopedic diseases: a review of the literature. Heliyon 9, e14961 (2023).

    Article  Google Scholar 

  80. Delalleau, A., Josse, G., Lagarde, J.-M., Zahouani, H. & Bergheau, J.-M. Characterization of the mechanical properties of skin by inverse analysis combined with the indentation test. J. Biomech. 39, 1603–1610 (2006).

    Article  Google Scholar 

  81. Jemec, G. B., Selvaag, E., Ågren, M. & Wulf, H. C. Measurement of the mechanical properties of skin with ballistometer and suction cup. Skin Res. Technol. 7, 122–126 (2001).

    Article  Google Scholar 

  82. Song, E. et al. Miniaturized electromechanical devices for the characterization of the biomechanics of deep tissue. Nat. Biomed. Eng. 5, 759–771 (2021).

    Article  Google Scholar 

  83. Lin, M., Hu, H., Zhou, S. & Xu, S. Soft wearable devices for deep-tissue sensing. Nat. Rev. Mater. 7, 850–869 (2022).

    Article  Google Scholar 

  84. Selvaraj, E. A. et al. Diagnostic accuracy of elastography and magnetic resonance imaging in patients with NAFLD: a systematic review and meta-analysis. J. Hepatol. 75, 770–785 (2021).

    Article  Google Scholar 

  85. Lee, K. et al. Mechano-acoustic sensing of physiological processes and body motions via a soft wireless device placed at the suprasternal notch. Nat. Biomed. Eng. 4, 148–158 (2020).

    Article  Google Scholar 

  86. Yoo, J.-Y. et al. Wireless broadband acousto-mechanical sensing system for continuous physiological monitoring. Nat. Med. 29, 3137–3148 (2023). This article reports an acousto-mechanical sensing network for continuous monitoring of respiratory airflow and intestinal motility in neonates in intensive care.

    Article  Google Scholar 

  87. Meng, K. et al. Wearable pressure sensors for pulse wave monitoring. Adv. Mater. 34, 2109357 (2022).

    Article  Google Scholar 

  88. Sunwoo, S.-H. et al. Soft bioelectronics for the management of cardiovascular diseases. Nat. Rev. Bioeng. 2, 8–24 (2024).

    Article  Google Scholar 

  89. Min, S. et al. Wearable blood pressure sensors for cardiovascular monitoring and machine learning algorithms for blood pressure estimation. Nat. Rev. Cardiol. 22, 629–648 (2025).

    Article  Google Scholar 

  90. Wang, C. et al. Monitoring of the central blood pressure waveform via a conformal ultrasonic device. Nat. Biomed. Eng. 2, 687–695 (2018).

    Article  Google Scholar 

  91. Zhao, T. Y. et al. Blood–wall fluttering instability as a physiomarker of the progression of thoracic aortic aneurysms. Nat. Biomed. Eng. 7, 1614–1626 (2023). This article reports the analysis of blood vessel biomechanics by MRI, proposing a flutter-instability parameter as a physiomarker for thoracic aortic aneurysm progression.

    Article  Google Scholar 

  92. Bar-Zion, A. et al. Acoustically triggered mechanotherapy using genetically encoded gas vesicles. Nat. Nanotechnol. 16, 1403–1412 (2021).

    Article  Google Scholar 

  93. Ricotti, V. et al. Wearable full-body motion tracking of activities of daily living predicts disease trajectory in Duchenne muscular dystrophy. Nat. Med. 29, 95–103 (2023).

    Article  Google Scholar 

  94. Toymus, A. T. et al. An integrated and flexible ultrasonic device for continuous bladder volume monitoring. Nat. Commun. 15, 7216 (2024).

    Article  Google Scholar 

  95. Dagdeviren, C. et al. Flexible piezoelectric devices for gastrointestinal motility sensing. Nat. Biomed. Eng. 1, 807–817 (2017).

    Article  Google Scholar 

  96. Liu, S., Rao, Y., Jang, H., Tan, P. & Lu, N. Strategies for body-conformable electronics. Matter 5, 1104–1136 (2022).

    Article  Google Scholar 

  97. Lenk, C. et al. Neuromorphic acoustic sensing using an adaptive microelectromechanical cochlea with integrated feedback. Nat. Electron. 6, 370–380 (2023).

    Article  Google Scholar 

  98. Kim, D.-H. et al. Stretchable and foldable silicon integrated circuits. Science 320, 507–511 (2008).

    Article  Google Scholar 

  99. Kim, D.-H. et al. Epidermal electronics. Science 333, 838–843 (2011).

    Article  Google Scholar 

  100. Lin, M. et al. A fully integrated wearable ultrasound system to monitor deep tissues in moving subjects. Nat. Biotechnol. 42, 448–457 (2024). This article reports a fully integrated wearable ultrasound system for continuous monitoring of blood flow dynamics in moving individuals.

    Article  Google Scholar 

  101. Li, P. et al. Monolithic silicon for high spatiotemporal translational photostimulation. Nature 626, 990–998 (2024).

    Article  Google Scholar 

  102. Jiang, Y. et al. Topological supramolecular network enabled high-conductivity, stretchable organic bioelectronics. Science 375, 1411–1417 (2022).

    Article  Google Scholar 

  103. Yuk, H., Lu, B. & Zhao, X. Hydrogel bioelectronics. Chem. Soc. Rev. 48, 1642–1667 (2019).

    Article  Google Scholar 

  104. Root, S. E., Savagatrup, S., Printz, A. D., Rodriquez, D. & Lipomi, D. J. Mechanical properties of organic semiconductors for stretchable, highly flexible, and mechanically robust electronics. Chem. Rev. 117, 6467–6499 (2017).

    Article  Google Scholar 

  105. Cho, C. et al. Strain-resilient electrical functionality in thin-film metal electrodes using two-dimensional interlayers. Nat. Electron. 4, 126–133 (2021).

    Article  Google Scholar 

  106. Yang, Y. et al. Wireless multilateral devices for optogenetic studies of individual and social behaviors. Nat. Neurosci. 24, 1035–1045 (2021).

    Article  Google Scholar 

  107. Widlund, T., Yang, S., Hsu, Y.-Y. & Lu, N. Stretchability and compliance of freestanding serpentine-shaped ribbons. Int. J. Solids Struct. 51, 4026–4037 (2014).

    Article  Google Scholar 

  108. Tian, L. et al. Large-area MRI-compatible epidermal electronic interfaces for prosthetic control and cognitive monitoring. Nat. Biomed. Eng. 3, 194–205 (2019).

    Article  Google Scholar 

  109. Lanzara, G., Salowitz, N., Guo, Z. & Chang, F.-K. A spider-web-like highly expandable sensor network for multifunctional materials. Adv. Mater. 22, 4643–4648 (2010).

    Article  Google Scholar 

  110. Kang, J., Tok, J. B. H. & Bao, Z. Self-healing soft electronics. Nat. Electron. 2, 144–150 (2019).

    Article  Google Scholar 

  111. Yin, J., Wang, S., Tat, T. & Chen, J. Motion artefact management for soft bioelectronics. Nat. Rev. Bioeng. 2, 541–558 (2024).

    Article  Google Scholar 

  112. Chung, H. U. et al. Skin-interfaced biosensors for advanced wireless physiological monitoring in neonatal and pediatric intensive-care units. Nat. Med. 26, 418–429 (2020).

    Article  Google Scholar 

  113. Kang, Y. J. et al. Soft skin-interfaced mechano-acoustic sensors for real-time monitoring and patient feedback on respiratory and swallowing biomechanics. NPJ Digit. Med. 5, 147 (2022).

    Article  Google Scholar 

  114. Boutry, C. M. et al. Biodegradable and flexible arterial-pulse sensor for the wireless monitoring of blood flow. Nat. Biomed. Eng. 3, 47–57 (2019). This article reports a biodegradable implantable sensor for wireless monitoring of blood flow dynamics.

    Article  Google Scholar 

  115. Zhao, X. et al. Permanent fluidic magnets for liquid bioelectronics. Nat. Mater. 23, 703–710 (2024). This article introduces a permanent fluidic magnet with sustained magnetization for highly sensitive biomechanical monitoring.

    Article  Google Scholar 

  116. Wu, P.-H. et al. A comparison of methods to assess cell mechanical properties. Nat. Methods 15, 491–498 (2018).

    Article  Google Scholar 

  117. Darling, E. M. & Di Carlo, D. High-throughput assessment of cellular mechanical properties. Annu. Rev. Biomed. Eng. 17, 35–62 (2015).

    Article  Google Scholar 

  118. Jiang, K. et al. Deleterious mechanical deformation selects mechanoresilient cancer cells with enhanced proliferation and chemoresistance. Adv. Sci. 10, e2201663 (2023).

    Article  Google Scholar 

  119. Ho, C.-M. & Tai, Y.-C. Micro-electro-mechanical-systems (MEMS) and fluid flows. Annu. Rev. Fluid Mech. 30, 579–612 (1998).

    Article  Google Scholar 

  120. Gossett, D. R. et al. Hydrodynamic stretching of single cells for large population mechanical phenotyping. Proc. Natl. Acad. Sci. USA 109, 7630–7635 (2012).

    Article  Google Scholar 

  121. Tse, H. T. K. et al. Quantitative diagnosis of malignant pleural effusions by single-cell mechanophenotyping. Sci. Transl. Med. 5, 212ra163 (2013). This article reports single-cell mechanophenotyping to quantitatively assess cellular mechanical properties, improving the diagnosis of malignant pleural effusions.

    Article  Google Scholar 

  122. Nagrath, S. et al. Isolation of rare circulating tumour cells in cancer patients by microchip technology. Nature 450, 1235–1239 (2007).

    Article  Google Scholar 

  123. Li, P. et al. Acoustic separation of circulating tumor cells. Proc. Natl Acad. Sci. USA 112, 4970–4975 (2015).

    Article  Google Scholar 

  124. Teh, S.-Y., Lin, R., Hung, L.-H. & Lee, A. P. Droplet microfluidics. Lab Chip 8, 198–220 (2008).

    Article  Google Scholar 

  125. Utada, A. S. et al. Monodisperse double emulsions generated from a microcapillary device. Science 308, 537–541 (2005).

    Article  Google Scholar 

  126. Thorsen, T., Roberts, R. W., Arnold, F. H. & Quake, S. R. Dynamic pattern formation in a vesicle-generating microfluidic device. Phys. Rev. Lett. 86, 4163–4166 (2001).

    Article  Google Scholar 

  127. Guedes, A. F. et al. Atomic force microscopy as a tool to evaluate the risk of cardiovascular diseases in patients. Nat. Nanotechnol. 11, 687–692 (2016).

    Article  Google Scholar 

  128. Català-Castro, F. et al. Measuring age-dependent viscoelasticity of organelles, cells and organisms with time-shared optical tweezer microrheology. Nat. Nanotechnol. 20, 411–420 (2025).

    Article  Google Scholar 

  129. Kollert, M. R. et al. Water and ions binding to extracellular matrix drives stress relaxation, aiding MRI detection of swelling-associated pathology. Nat. Biomed. Eng. 9, 772–786 (2025).

    Article  Google Scholar 

  130. Bao, G. & Suresh, S. Cell and molecular mechanics of biological materials. Nat. Mater. 2, 715–725 (2003).

    Article  Google Scholar 

  131. Nunes Vicente, F., Chen, T., Rossier, O. & Giannone, G. Novel imaging methods and force probes for molecular mechanobiology of cytoskeleton and adhesion. Trends Cell Biol. 33, 204–220 (2023).

    Article  Google Scholar 

  132. Wang, Y., Shyy, J. Y.-J. & Chien, S. Fluorescence proteins, live-cell imaging, and mechanobiology: seeing is believing. Annu. Rev. Biomed. Eng. 10, 1–38 (2008).

    Article  Google Scholar 

  133. Fischer, L. S., Rangarajan, S., Sadhanasatish, T. & Grashoff, C. Molecular force measurement with tension sensors. Annu. Rev. Biophys. 50, 595–616 (2021).

    Article  Google Scholar 

  134. Chabria, M., Hertig, S., Smith, M. L. & Vogel, V. Stretching fibronectin fibres disrupts binding of bacterial adhesins by physically destroying an epitope. Nat. Commun. 1, 135 (2010).

    Article  Google Scholar 

  135. Hu, Y. et al. Quantifying T cell receptor mechanics at membrane junctions using DNA origami tension sensors. Nat. Nanotechnol. 19, 1674–1685 (2024).

    Article  Google Scholar 

  136. Zhou, Y. et al. Giant magnetoelastic effect in soft systems for bioelectronics. Nat. Mater. 20, 1670–1676 (2021). This article reports the giant magnetoelastic effect in soft material systems for biomechanical sensing.

    Article  Google Scholar 

  137. Zhao, X. et al. Soft fibers with magnetoelasticity for wearable electronics. Nat. Commun. 12, 6755 (2021).

    Article  Google Scholar 

  138. Zhou, T. et al. 3D printable high-performance conducting polymer hydrogel for all-hydrogel bioelectronic interfaces. Nat. Mater. 22, 895–902 (2023).

    Article  Google Scholar 

  139. Wu, S. J. & Zhao, X. Bioadhesive technology platforms. Chem. Rev. 123, 14084–14118 (2023).

    Article  Google Scholar 

  140. Taki, M., Yamashita, T., Yatabe, K. & Vogel, V. Mechano-chromic protein–polymer hybrid hydrogel to visualize mechanical strain. Soft Matter 15, 9388–9393 (2019).

    Article  Google Scholar 

  141. Issatayeva, A., Beisenova, A., Tosi, D. & Molardi, C. Fiber-optic based smart textiles for real-time monitoring of breathing rate. Sensors 20, 3408 (2020).

    Article  Google Scholar 

  142. Woo, S. L. Y., Abramowitch, S. D., Kilger, R. & Liang, R. Biomechanics of knee ligaments: injury, healing, and repair. J. Biomech. 39, 1–20 (2006).

    Article  Google Scholar 

  143. Hopkins, D. et al. Computational modeling of revision total hip arthroplasty involving acetabular defects: a systematic review. J. Orthop. Res. 42, 2249–2263 (2024).

    Article  Google Scholar 

  144. Sun, B. et al. A 3D-bioprinted dual growth factor-releasing intervertebral disc scaffold induces nucleus pulposus and annulus fibrosus reconstruction. Bioact. Mater. 6, 179–190 (2021).

    Google Scholar 

  145. Wu, C. et al. A machine learning-based multiscale model to predict bone formation in scaffolds. Nat. Computational Sci. 1, 532–541 (2021).

    Article  Google Scholar 

  146. Chmielewska, A. & Dean, D. The role of stiffness-matching in avoiding stress shielding-induced bone loss and stress concentration-induced skeletal reconstruction device failure. Acta Biomater. 173, 51–65 (2024).

    Article  Google Scholar 

  147. Kim, J. et al. Soft robotic apparel to avert freezing of gait in Parkinson’s disease. Nat. Med. 30, 177–185 (2024). This article reports an exosuit that mechanically augments hip flexion to reliably prevent freezing of gait in individuals with Parkinson’s disease.

    Article  Google Scholar 

  148. Proietti, T. et al. Restoring arm function with a soft robotic wearable for individuals with amyotrophic lateral sclerosis. Sci. Transl. Med. 15, eadd1504 (2023).

    Article  Google Scholar 

  149. Awad, L. N. et al. A soft robotic exosuit improves walking in patients after stroke. Sci. Transl. Med. 9, eaai9084 (2017).

    Article  Google Scholar 

  150. Cheung, J. T.-M., Zhang, M., Leung, A. K.-L. & Fan, Y.-B. Three-dimensional finite element analysis of the foot during standing — a material sensitivity study. J. Biomech. 38, 1045–1054 (2005).

    Article  Google Scholar 

  151. Seth, A. et al. OpenSim: simulating musculoskeletal dynamics and neuromuscular control to study human and animal movement. PLoS Comput. Biol. 14, e1006223 (2018).

    Article  Google Scholar 

  152. Chen, Y. N., Wu, Y. N. & Yang, B. S. The neuromuscular control for lower limb exoskeleton- a 50-year perspective. J. Biomech. 158, 111738 (2023).

    Article  Google Scholar 

  153. Zhang, X., Chan, F. K., Parthasarathy, T. & Gazzola, M. Modeling and simulation of complex dynamic musculoskeletal architectures. Nat. Commun. 10, 4825 (2019).

    Article  Google Scholar 

  154. Ding, X., Sha, D., Sun, K. & Fan, Y. Biomechanical insights into the development and optimization of small-diameter vascular grafts. Acta Biomater. https://doi.org/10.1016/j.actbio.2025.04.028 (2025).

    Article  Google Scholar 

  155. Chen, R., Canales, A. & Anikeeva, P. Neural recording and modulation technologies. Nat. Rev. Mater. 2, 16093 (2017).

    Article  Google Scholar 

  156. Kim, D. H. et al. Dissolvable films of silk fibroin for ultrathin conformal bio-integrated electronics. Nat. Mater. 9, 511–517 (2010).

    Article  Google Scholar 

  157. Liu, Y. et al. Soft and elastic hydrogel-based microelectronics for localized low-voltage neuromodulation. Nat. Biomed. Eng. 3, 58–68 (2019).

    Article  Google Scholar 

  158. Fioretta, E. S. et al. Next-generation tissue-engineered heart valves with repair, remodelling and regeneration capacity. Nat. Rev. Cardiol. 18, 92–116 (2021).

    Article  Google Scholar 

  159. Ifkovits, J. L. et al. Injectable hydrogel properties influence infarct expansion and extent of postinfarction left ventricular remodeling in an ovine model. Proc. Natl Acad. Sci. USA 107, 11507–11512 (2010).

    Article  Google Scholar 

  160. Ryu, H. et al. Materials and design approaches for a fully bioresorbable, electrically conductive and mechanically compliant cardiac patch technology. Adv. Sci. 10, 2303429 (2023).

    Article  Google Scholar 

  161. Montgomery, M. et al. Flexible shape-memory scaffold for minimally invasive delivery of functional tissues. Nat. Mater. 16, 1038–1046 (2017).

    Article  Google Scholar 

  162. Lin, X. et al. A viscoelastic adhesive epicardial patch for treating myocardial infarction. Nat. Biomed. Eng. 3, 632–643 (2019).

    Article  Google Scholar 

  163. Uhler, C. & Shivashankar, G. V. Regulation of genome organization and gene expression by nuclear mechanotransduction. Nat. Rev. Mol. Cell Biol. 18, 717–727 (2017).

    Article  Google Scholar 

  164. Kalukula, Y., Stephens, A. D., Lammerding, J. & Gabriele, S. Mechanics and functional consequences of nuclear deformations. Nat. Rev. Mol. Cell Biol. 23, 583–602 (2022).

    Article  Google Scholar 

  165. Wang, N., Tytell, J. D. & Ingber, D. E. Mechanotransduction at a distance: mechanically coupling the extracellular matrix with the nucleus. Nat. Rev. Mol. Cell Biol. 10, 75–82 (2009).

    Article  Google Scholar 

  166. Hillsley, M. V. & Frangos, J. A. Review: Bone tissue engineering: the role of interstitial fluid flow. Biotechnol. Bioeng. 43, 573–581 (1994).

    Article  Google Scholar 

  167. Rutkowski, J. M. & Swartz, M. A. A driving force for change: interstitial flow as a morphoregulator. Trends Cell Biol. 17, 44–50 (2007).

    Article  Google Scholar 

  168. Du, H. et al. Tuning immunity through tissue mechanotransduction. Nat. Rev. Immunol. 23, 174–188 (2023).

    Article  Google Scholar 

  169. Mitragotri, S., Blankschtein, D. & Langer, R. Ultrasound-mediated transdermal protein delivery. Science 269, 850–853 (1995).

    Article  Google Scholar 

  170. Wang, Y., Li, J., Zhou, J., Qiu, Y. & Song, J. Low-intensity pulsed ultrasound enhances bone marrow-derived stem cells-based periodontal regenerative therapies. Ultrasonics 121, 106678 (2022).

    Article  Google Scholar 

  171. Brugger, M. S. et al. Vibration enhanced cell growth induced by surface acoustic waves as in vitro wound-healing model. Proc. Natl. Acad. Sci. USA 117, 31603–31613 (2020).

    Article  Google Scholar 

  172. Zhou, X. et al. Improved human bone marrow mesenchymal stem cell osteogenesis in 3D bioprinted tissue scaffolds with low intensity pulsed ultrasound stimulation. Sci. Rep. 6, 32876 (2016).

    Article  Google Scholar 

  173. Busse, J. W. et al. Re-evaluation of low intensity pulsed ultrasound in treatment of tibial fractures (trust): randomized clinical trial. BMJ 355, i5351 (2016).

    Google Scholar 

  174. Liu, H. et al. Bone fracture healing under the intervention of a stretchable ultrasound array. ACS Nano 18, 19549–19560 (2024).

    Google Scholar 

  175. Maan, Z. N. et al. Noncontact, low-frequency ultrasound therapy enhances neovascularization and wound healing in diabetic mice. Plast. Reconstr. Surg. 134, 402e–411e (2014).

    Article  Google Scholar 

  176. de Oliveira Perrucini, P. D. et al. Anti-inflammatory and healing effects of pulsed ultrasound therapy on fibroblasts. Am. J. Phys. Med. Rehabil. 99, 19–25 (2020).

    Article  Google Scholar 

  177. Wang, X., Stefanello, S. T., Shahin, V. & Qian, Y. From mechanoelectric conversion to tissue regeneration: translational progress in piezoelectric materials. Adv. Mater. 37, e2417564 (2025).

    Article  Google Scholar 

  178. Anestiadou, E. et al. Comparison of negative pressure wound therapy systems and conventional non-pressure dressings on surgical site infection rate after stoma reversal: Systematic review and meta-analysis of randomized controlled trials. J. Clin. Med. 14, 1654 (2025).

    Article  Google Scholar 

  179. Shou, Y. et al. Mechano-activated cell therapy for accelerated diabetic wound healing. Adv. Mater. 35, 2304638 (2023).

    Article  Google Scholar 

  180. Mascharak, S. et al. Preventing engrailed-1 activation in fibroblasts yields wound regeneration without scarring. Science 372, eaba2374 (2021).

    Article  Google Scholar 

  181. Zhao, C., Park, J., Root, S. E. & Bao, Z. Skin-inspired soft bioelectronic materials, devices and systems. Nat. Rev. Bioeng. 2, 671–690 (2024).

    Article  Google Scholar 

  182. Yu, X. et al. Skin-integrated wireless haptic interfaces for virtual and augmented reality. Nature 575, 473–479 (2019).

    Article  Google Scholar 

  183. Kim, D. et al. Actuating compact wearable augmented reality devices by multifunctional artificial muscle. Nat. Commun. 13, 4155 (2022).

    Article  Google Scholar 

  184. Huang, Y. et al. A skin-integrated multimodal haptic interface for immersive tactile feedback. Nat. Electron. 6, 1020–1031 (2023).

    Article  Google Scholar 

  185. Jung, Y. H. et al. A wireless haptic interface for programmable patterns of touch across large areas of the skin. Nat. Electronics 5, 374–385 (2022).

    Article  Google Scholar 

  186. Kim, J.-H. et al. A wirelessly programmable, skin-integrated thermo-haptic stimulator system for virtual reality. Proc. Natl. Acad. Sci. USA 121, e2404007121 (2024).

    Article  Google Scholar 

  187. Gozzi, N. et al. Wearable non-invasive neuroprosthesis for targeted sensory restoration in neuropathy. Nat. Commun. 15, 10840 (2024).

    Article  Google Scholar 

  188. Petrini, F. M. et al. Sensory feedback restoration in leg amputees improves walking speed, metabolic cost and phantom pain. Nat. Med. 25, 1356–1363 (2019).

    Article  Google Scholar 

  189. Charkhkar, H. et al. High-density peripheral nerve cuffs restore natural sensation to individuals with lower-limb amputations. J. Neural Eng. 15, 056002 (2018).

    Article  Google Scholar 

  190. Song, H. et al. Continuous neural control of a bionic limb restores biomimetic gait after amputation. Nat. Med. 30, 2010–2019 (2024).

    Article  Google Scholar 

  191. Abad, S.-A., Herzig, N., Raitt, D., Koltzenburg, M. & Wurdemann, H. Bioinspired adaptable multiplanar mechano-vibrotactile haptic system. Nat. Commun. 15, 7631 (2024).

    Article  Google Scholar 

  192. Greenspon, C. M. et al. Evoking stable and precise tactile sensations via multi-electrode intracortical microstimulation of the somatosensory cortex. Nat. Biomed. Eng. 9, 935–951 (2025).

    Article  Google Scholar 

  193. Ryu, H. et al. Self-rechargeable cardiac pacemaker system with triboelectric nanogenerators. Nat. Commun. 12, 4374 (2021).

    Article  Google Scholar 

  194. Li, N. et al. Direct powering a real cardiac pacemaker by natural energy of a heartbeat. ACS Nano 13, 2822–2830 (2019).

    Article  Google Scholar 

  195. Shi, B., Li, Z. & Fan, Y. Implantable energy-harvesting devices. Adv. Mater. 30, 1801511 (2018).

    Article  Google Scholar 

  196. Liu, Z. et al. A self-powered intracardiac pacemaker in swine model. Nat. Commun. 15, 507 (2024).

    Article  Google Scholar 

  197. Sun, H. et al. Liquid-based encapsulation for implantable bioelectronics across broad pH environments. Nat. Commun. 16, 1019 (2025).

    Article  Google Scholar 

  198. Yi, Z. et al. A battery-and leadless heart-worn pacemaker strategy. Adv. Funct. Mater. 30, 2000477 (2020).

    Article  Google Scholar 

  199. Ouyang, H. et al. Symbiotic cardiac pacemaker. Nat. Commun. 10, 1821 (2019).

    Article  Google Scholar 

  200. Rahne, T. & Plontke, S. K. Systematic and audiological indication criteria for bone conduction devices and active middle ear implants. Hearing Res. 421, 108424 (2022).

    Article  Google Scholar 

  201. Welss, T., Basketter, D. A. & Schröder, K. R. In vitro skin irritation: facts and future. State of the art review of mechanisms and models. Toxicol. In Vitro 18, 231–243 (2004).

    Article  Google Scholar 

  202. Willenborg, K., Avallone, E., Maier, H., Lenarz, T. & Busch, S. A new active osseointegrated implant system in patients with single-sided deafness. Audiol. Neurotol. 27, 83–92 (2022).

    Article  Google Scholar 

  203. Huber, A. et al. The bonebridge: preclinical evaluation of a new transcutaneously-activated bone anchored hearing device. Hearing Res. 301, 93–99 (2013).

    Article  Google Scholar 

  204. Cuda, D. et al. Improving quality of life in the elderly: hearing loss treatment with cochlear implants. BMC Geriatr. 24, 16 (2024).

    Article  Google Scholar 

  205. Essaid, B., Kheddar, H., Batel, N., Chowdhury, M. E. H. & Lakas, A. Artificial intelligence for cochlear implants: review of strategies, challenges, and perspectives. IEEE Access 12, 119015–119038 (2024).

    Article  Google Scholar 

  206. Moshizi, S. A. et al. Recent advancements in bioelectronic devices to interface with the peripheral vestibular system. Biosens. Bioelectron. 214, 114521 (2022).

    Article  Google Scholar 

  207. Radisic, M., Marsano, A., Maidhof, R., Wang, Y. & Vunjak-Novakovic, G. Cardiac tissue engineering using perfusion bioreactor systems. Nat. Protoc. 3, 719–738 (2008).

    Article  Google Scholar 

  208. Niklason, L. et al. Functional arteries grown in vitro. Science 284, 489–493 (1999).

    Article  Google Scholar 

  209. Tamargo, I. A., Baek, K. I., Kim, Y., Park, C. & Jo, H. Flow-induced reprogramming of endothelial cells in atherosclerosis. Nat. Rev. Cardiol. 20, 738–753 (2023).

    Article  Google Scholar 

  210. Li, S., Sengupta, D. & Chien, S. Vascular tissue engineering: from in vitro to in situ. Wiley Interdiscip. Rev. Syst. Biol. Med. 6, 61–76 (2014).

    Article  Google Scholar 

  211. Lee, J. K. et al. Tension stimulation drives tissue formation in scaffold-free systems. Nat. Mater. 16, 864–873 (2017).

    Article  Google Scholar 

  212. O’Conor, C. J., Case, N. & Guilak, F. Mechanical regulation of chondrogenesis. Stem Cell Res. Ther. 4, 61 (2013).

    Article  Google Scholar 

  213. Soubrier, A. et al. A novel intervertebral disc bioreactor system for studying clinically based active dynamic unloading combining biological and biomechanical outcomes. Eur. Cell Mater. 50, 1–19 (2025).

    Article  Google Scholar 

  214. Huh, D. et al. Reconstituting organ-level lung functions on a chip. Science 328, 1662–1668 (2010). This article reports the first functional ‘lung-on-a-chip’ device that stimulates mechanical cues of breathing motions and provides an alveolar–capillary interface.

    Article  Google Scholar 

  215. Wang, P. et al. Blood–brain barrier injury and neuroinflammation induced by SARS-CoV-2 in a lung–brain microphysiological system. Nat. Biomed. Eng. 8, 1053–1068 (2024).

    Article  Google Scholar 

  216. Sarkar, N., Bhumiratana, S., Geris, L., Papantoniou, I. & Grayson, W. L. Bioreactors for engineering patient-specific tissue grafts. Nat. Rev. Bioeng. 1, 361–377 (2023).

    Article  Google Scholar 

  217. Tiburcy, M. et al. Defined engineered human myocardium with advanced maturation for applications in heart failure modeling and repair. Circulation 135, 1832–1847 (2017).

    Article  Google Scholar 

  218. Vining, K. H. & Mooney, D. J. Mechanical forces direct stem cell behaviour in development and regeneration. Nat. Rev. Mol. Cell Biol. 18, 728–742 (2017).

    Article  Google Scholar 

  219. Fang, J. et al. Engineering biomaterials with micro/nanotechnologies for cell reprogramming. ACS Nano 14, 1296–1318 (2020).

    Article  Google Scholar 

  220. Janmey, P. A., Fletcher, D. A. & Reinhart-King, C. A. Stiffness sensing by cells. Physiological Rev. 100, 695–724 (2020).

    Article  Google Scholar 

  221. Kurpinski, K., Chu, J., Hashi, C. & Li, S. Anisotropic mechanosensing by mesenchymal stem cells. Proc. Natl Acad. Sci. USA 103, 16095–16100 (2006).

    Article  Google Scholar 

  222. Terraciano, V. et al. Differential response of adult and embryonic mesenchymal progenitor cells to mechanical compression in hydrogels. Stem Cell 25, 2730–2738 (2007).

    Article  Google Scholar 

  223. Engler, A. J., Sen, S., Sweeney, H. L. & Discher, D. E. Matrix elasticity directs stem cell lineage specification. Cell 126, 677–689 (2006). This article reports the differential effects of matrix elasticity on the differentiation of stem cells into different lineages.

    Article  Google Scholar 

  224. Saha, K. et al. Substrate modulus directs neural stem cell behavior. Biophys. J. 95, 4426–4438 (2008).

    Article  Google Scholar 

  225. Park, J. S. et al. The effect of matrix stiffness on the differentiation of mesenchymal stem cells in response to TGF-β. Biomaterials 32, 3921–3930 (2011).

    Article  Google Scholar 

  226. Cameron, A. R., Frith, J. E., Gomez, G. A., Yap, A. S. & Cooper-White, J. J. The effect of time-dependent deformation of viscoelastic hydrogels on myogenic induction and rac1 activity in mesenchymal stem cells. Biomaterials 35, 1857–1868 (2014).

    Article  Google Scholar 

  227. Chaudhuri, O. et al. Hydrogels with tunable stress relaxation regulate stem cell fate and activity. Nat. Mater. 15, 326–334 (2016). This article reports that matrix viscoelasticity is a crucial and independent mechanical regulator of cell behaviour, beyond stiffness.

    Article  Google Scholar 

  228. Dalby, M. J. et al. The control of human mesenchymal cell differentiation using nanoscale symmetry and disorder. Nat. Mater. 6, 997–1003 (2007).

    Article  Google Scholar 

  229. Wang, X. et al. Chromatin reprogramming and bone regeneration in vitro and in vivo via the microtopography-induced constriction of cell nuclei. Nat. Biomed. Eng. 7, 1514–1529 (2023).

    Article  Google Scholar 

  230. Xue, X. et al. Mechanics-guided embryonic patterning of neuroectoderm tissue from human pluripotent stem cells. Nat. Mater. 17, 633–641 (2018).

    Article  Google Scholar 

  231. Pérez-González, C. et al. Mechanical compartmentalization of the intestinal organoid enables crypt folding and collective cell migration. Nat. Cell Biol. 23, 745–757 (2021).

    Article  Google Scholar 

  232. Takahashi, K. & Yamanaka, S. A decade of transcription factor-mediated reprogramming to pluripotency. Nat. Rev. Mol. Cell Biol. 17, 183–193 (2016).

    Article  Google Scholar 

  233. Srivastava, D. & DeWitt, N. In vivo cellular reprogramming: the next generation. Cell 166, 1386–1396 (2016).

    Article  Google Scholar 

  234. Papp, B. & Plath, K. Epigenetics of reprogramming to induced pluripotency. Cell 152, 1324–1343 (2013).

    Article  Google Scholar 

  235. Schlaeger, T. M. et al. A comparison of non-integrating reprogramming methods. Nat. Biotechnol. 33, 58–63 (2015).

    Article  Google Scholar 

  236. Lammerding, J., Engler, A. J. & Kamm, R. Mechanobiology of the cell nucleus. APL Bioeng. 6, 040401 (2022).

    Article  Google Scholar 

  237. Downing, T. L. et al. Biophysical regulation of epigenetic state and cell reprogramming. Nat. Mater. 12, 1154–1162 (2013).

    Article  Google Scholar 

  238. Jain, N., Iyer, K. V., Kumar, A. & Shivashankar, G. V. Cell geometric constraints induce modular gene-expression patterns via redistribution of HDAC3 regulated by actomyosin contractility. Proc. Natl Acad. Sci. USA 110, 11349–11354 (2013).

    Article  Google Scholar 

  239. Song, Y. et al. Transient nuclear deformation primes epigenetic state and promotes cell reprogramming. Nat. Mater. 21, 1191–1199 (2022). This article reports the direct effect of mechanical deformation on chromatin and a high-throughput microfluidic system for epigenetic priming and cell reprogramming.

    Article  Google Scholar 

  240. Heo, S. J. et al. Aberrant chromatin reorganization in cells from diseased fibrous connective tissue in response to altered chemomechanical cues. Nat. Biomed. Eng. 7, 177–191 (2023).

    Article  Google Scholar 

  241. Kant, A. et al. Active transcription and epigenetic reactions synergistically regulate meso-scale genomic organization. Nat. Commun. 15, 4338 (2024).

    Article  Google Scholar 

  242. Lomakin, A. J. et al. The nucleus acts as a ruler tailoring cell responses to spatial constraints. Science 370, eaba2894 (2020).

    Article  Google Scholar 

  243. Roy, B. et al. Fibroblast rejuvenation by mechanical reprogramming and redifferentiation. Proc. Natl Acad. Sci. USA 117, 10131–10141 (2020).

    Article  Google Scholar 

  244. Alisafaei, F. et al. Tension anisotropy drives fibroblast phenotypic transition by self-reinforcing cell-extracellular matrix mechanical feedback. Nat. Mater. 24, 955–965 (2025).

    Article  Google Scholar 

  245. Song, Y. et al. Biphasic regulation of epigenetic state by matrix stiffness during cell reprogramming. Sci. Adv. 10, eadk0639 (2024).

    Article  Google Scholar 

  246. Wu, Y. et al. Viscoelastic extracellular matrix enhances epigenetic remodeling and cellular plasticity. Nat. Commun. 16, 4054 (2025).

    Article  Google Scholar 

  247. Zhu, C., Chen, W., Lou, J., Rittase, W. & Li, K. Mechanosensing through immunoreceptors. Nat. Immunol. 20, 1269–1278 (2019).

    Article  Google Scholar 

  248. Kim, S. T. et al. The αβ T cell receptor is an anisotropic mechanosensor. J. Biol. Chem. 284, 31028–31037 (2009).

    Article  Google Scholar 

  249. Liu, B., Chen, W., Evavold, Brian, D. & Zhu, C. Accumulation of dynamic catch bonds between TCR and agonist peptide-MHC triggers T cell signaling. Cell 157, 357–368 (2014).

    Article  Google Scholar 

  250. Basu, R. et al. Cytotoxic T cells use mechanical force to potentiate target cell killing. Cell 165, 100–110 (2016).

    Article  Google Scholar 

  251. Cheung, A. S., Zhang, D. K. Y., Koshy, S. T. & Mooney, D. J. Scaffolds that mimic antigen-presenting cells enable ex vivo expansion of primary T cells. Nat. Biotechnol. 36, 160–169 (2018).

    Article  Google Scholar 

  252. Agarwalla, P. et al. Bioinstructive implantable scaffolds for rapid in vivo manufacture and release of CAR-T cells. Nat. Biotechnol. 40, 1250–1258 (2022).

    Article  Google Scholar 

  253. Shi, L., Lim, J. Y. & Kam, L. C. Substrate stiffness enhances human regulatory T cell induction and metabolism. Biomaterials 292, 121928 (2023).

    Article  Google Scholar 

  254. Liu, Z. et al. Viscoelastic synthetic antigen-presenting cells for augmenting the potency of cancer therapies. Nat. Biomed. Eng. 8, 1615–1633 (2024). This article reports that the viscoelasticity of artificial cells can modulate the stemness and ratio of CD8+ to CD4+ cells during CAR-T cell manufacturing.

    Article  Google Scholar 

  255. Adu-Berchie, K. et al. Generation of functionally distinct T-cell populations by altering the viscoelasticity of their extracellular matrix. Nat. Biomed. Eng. 7, 1374–1391 (2023).

    Article  Google Scholar 

  256. Hickey, J. W. et al. Engineering an artificial T-cell stimulating matrix for immunotherapy. Adv. Mater. 31, e1807359 (2019).

    Article  Google Scholar 

  257. Zhu, E. et al. Biomimetic cell stimulation with a graphene oxide antigen-presenting platform for developing T cell-based therapies. Nat. Nanotechnol. 19, 1914–1922 (2024).

    Article  Google Scholar 

  258. Huang, X. et al. DNA scaffolds enable efficient and tunable functionalization of biomaterials for immune cell modulation. Nat. Nanotechnol. 16, 214–223 (2021).

    Article  Google Scholar 

  259. Oh, J. et al. The effect of the nanoparticle shape on T cell activation. Small 18, e2107373 (2022).

    Article  Google Scholar 

  260. Li, Y.-R., Liu, Z. & Zhu, E. Biomaterials mimicking immunological synapses for enhanced T cell activation in CAR-T therapy. Sci. Bull. 70, 3103–3105 (2025).

    Article  Google Scholar 

  261. Natkanski, E. et al. B cells use mechanical energy to discriminate antigen affinities. Science 340, 1587–1590 (2013).

    Article  Google Scholar 

  262. González, C. et al. Nanobody-CD16 catch bond reveals NK cell mechanosensitivity. Biophys. J. 116, 1516–1526 (2019).

    Article  Google Scholar 

  263. Jain, N., Moeller, J. & Vogel, V. Mechanobiology of macrophages: how physical factors coregulate macrophage plasticity and phagocytosis. Annu. Rev. Biomed. Eng. 21, 267–297 (2019).

    Article  Google Scholar 

  264. Madden, L. R. et al. Proangiogenic scaffolds as functional templates for cardiac tissue engineering. Proc. Natl Acad. Sci. USA 107, 15211–15216 (2010).

    Article  Google Scholar 

  265. Meli, V. S. et al. Yap-mediated mechanotransduction tunes the macrophage inflammatory response. Sci. Adv. 6, eabb8471 (2020).

    Article  Google Scholar 

  266. Seet, C. S. et al. Generation of mature T cells from human hematopoietic stem and progenitor cells in artificial thymic organoids. Nat. Methods 14, 521–530 (2017).

    Article  Google Scholar 

  267. Stower, H. Maintaining and expanding HSCs. Nat. Med. 25, 1029 (2019).

    Google Scholar 

  268. Trotman-Grant, A. C. et al. Dl4-mubeads induce T cell lineage differentiation from stem cells in a stromal cell-free system. Nat. Commun. 12, 5023 (2021).

    Article  Google Scholar 

  269. Renkawitz, J. et al. Adaptive force transmission in amoeboid cell migration. Nat. Cell Biol. 11, 1438–1443 (2009).

    Article  Google Scholar 

  270. Paul, C. D., Mistriotis, P. & Konstantopoulos, K. Cancer cell motility: lessons from migration in confined spaces. Nat. Rev. Cancer 17, 131–140 (2017).

    Article  Google Scholar 

  271. Tharp, K. M. et al. Tumor-associated macrophages restrict CD8+ T cell function through collagen deposition and metabolic reprogramming of the breast cancer microenvironment. Nat. Cancer 5, 1045–1062 (2024).

    Article  Google Scholar 

  272. Fonta, C. M. et al. Infiltrating CD8+ T cells and M2 macrophages are retained in tumor matrix tracks enriched in low tension fibronectin fibers. Matrix Biol. 116, 1–27 (2023).

    Article  Google Scholar 

  273. Kumar, S. & Weaver, V. M. Mechanics, malignancy, and metastasis: the force journey of a tumor cell. Cancer Metastasis Rev. 28, 113–127 (2009).

    Article  Google Scholar 

  274. Zanotelli, M. R., Zhang, J. & Reinhart-King, C. A. Mechanoresponsive metabolism in cancer cell migration and metastasis. Cell Metab. 33, 1307–1321 (2021).

    Article  Google Scholar 

  275. Romani, P., Valcarcel-Jimenez, L., Frezza, C. & Dupont, S. Crosstalk between mechanotransduction and metabolism. Nat. Rev. Mol. Cell Biol. 22, 22–38 (2021).

    Article  Google Scholar 

  276. Zhang, J. et al. Osr2 functions as a biomechanical checkpoint to aggravate CD8+ T cell exhaustion in tumor. Cell 187, 3409–3426.e24 (2024).

    Article  Google Scholar 

  277. Liu, Y. et al. Cell softness prevents cytolytic T-cell killing of tumor-repopulating cells. Cancer Res. 81, 476–488 (2021).

    Article  Google Scholar 

  278. Kewen, L. A. et al. Cancer-cell stiffening via cholesterol depletion enhances adoptive T-cell immunotherapy. Nat. Biomed. Eng. 5, 1411–1425 (2021).

    Article  Google Scholar 

  279. Zhao, X. et al. Tuning T cell receptor sensitivity through catch bond engineering. Science 376, eabl5282 (2022).

    Article  Google Scholar 

  280. Liu, L. et al. Engineering sonogenetic echoback-CAR T cells. Cell 188 (10), 2621–2636 (2025). This article reports that CAR expression in T cells can be remotely activated by focused ultrasound to sustain antitumour activity.

    Article  Google Scholar 

  281. Gao, T. et al. Sonogenetics-controlled synthetic designer cells for cancer therapy in tumor mouse models. Cell Rep. Med. 5, 101513 (2024).

    Article  Google Scholar 

  282. Majedi, F. S. et al. Systemic enhancement of antitumour immunity by peritumourally implanted immunomodulatory macroporous scaffolds. Nat. Biomed. Eng. 7, 56–71 (2023).

    Article  Google Scholar 

  283. Lou, J. & Mooney, D. J. Chemical strategies to engineer hydrogels for cell culture. Nat. Rev. Chem. 6, 726–744 (2022).

    Article  Google Scholar 

  284. Kloxin, A. M., Kasko, A. M., Salinas, C. N. & Anseth, K. S. Photodegradable hydrogels for dynamic tuning of physical and chemical properties. Science 324, 59–63 (2009). This article reports photodegradable hydrogels with stiffness and biochemical cues that can be precisely modulated by light, introducing a tool for the spatiotemporal control of microenvironments.

    Article  Google Scholar 

  285. Sun, J. et al. Protein fibers with self-recoverable mechanical properties via dynamic imine chemistry. Nat. Commun. 14, 5348 (2023).

    Article  Google Scholar 

  286. Li, J. & Mooney, D. J. Designing hydrogels for controlled drug delivery. Nat. Rev. Mater. 1, 16071 (2016).

    Article  Google Scholar 

  287. Kong, D. C. et al. Control of polymer properties by entanglement: a review. Macromol. Mater. Eng. 306, 2100536 (2021).

    Article  Google Scholar 

  288. Liu, P. et al. Mechanically triggered on-demand degradation of polymers synthesized by radical polymerizations. Nat. Chem. 16, 1184–1192 (2024).

    Article  Google Scholar 

  289. Zhang, K., Feng, Q., Fang, Z., Gu, L. & Bian, L. Structurally dynamic hydrogels for biomedical applications: Pursuing a fine balance between macroscopic stability and microscopic dynamics. Chem. Rev. 121, 11149–11193 (2021).

    Article  Google Scholar 

  290. Hubbell, J. A. Immunoengineering a future of molecular, material, and cellular therapeutics. J. Immunol. 212, 167–168 (2024).

    Article  Google Scholar 

  291. Caprioli, M. et al. 3D-printed self-healing hydrogels via digital light processing. Nat. Commun. 12, 2462 (2021).

    Article  Google Scholar 

  292. Li, Y., Zhou, X., Sarkar, B., Gagnon-Lafrenais, N. & Cicoira, F. Recent progress on self-healable conducting polymers. Adv. Mater. 34, 2108932 (2022).

    Article  Google Scholar 

  293. Qin, H., Zhang, T., Li, N., Cong, H.-P. & Yu, S.-H. Anisotropic and self-healing hydrogels with multi-responsive actuating capability. Nat. Commun. 10, 2202 (2019).

    Article  Google Scholar 

  294. Loebel, C., Rodell, C. B., Chen, M. H. & Burdick, J. A. Shear-thinning and self-healing hydrogels as injectable therapeutics and for 3D-printing. Nat. Protoc. 12, 1521–1541 (2017).

    Article  Google Scholar 

  295. Truong, W. T., Su, Y., Meijer, J. T., Thordarson, P. & Braet, F. Self-assembled gels for biomedical applications. Chem. Asian J. 6, 30–42 (2011).

    Article  Google Scholar 

  296. Webber, M. J., Appel, E. A., Meijer, E. W. & Langer, R. Supramolecular biomaterials. Nat. Mater. 15, 13–26 (2016).

    Article  Google Scholar 

  297. Martino, M. M. et al. Growth factors engineered for super-affinity to the extracellular matrix enhance tissue healing. Science 343, 885–888 (2014).

    Article  Google Scholar 

  298. Mohanraj, B. et al. Mechanically-activated microcapsules for ‘on-demand’ drug delivery in dynamically loaded musculoskeletal tissues. Adv. Funct. Mater. 29, 1807909 (2019).

    Article  Google Scholar 

  299. Li, Y. et al. Magnetic hydrogels and their potential biomedical applications. Adv. Funct. Mater. 23, 660–672 (2013).

    Article  Google Scholar 

  300. Jin, F. et al. Biofeedback electrostimulation for bionic and long-lasting neural modulation. Nat. Commun. 13, 5302 (2022).

    Article  Google Scholar 

  301. Vinikoor, T. et al. Injectable and biodegradable piezoelectric hydrogel for osteoarthritis treatment. Nat. Commun. 14, 6257 (2023).

    Article  Google Scholar 

  302. Kong, Y. et al. Regulation of stem cell fate using nanostructure-mediated physical signals. Chem. Soc. Rev. 50, 12828–12872 (2021).

    Article  Google Scholar 

  303. Zhang, X. et al. Skin-like cryogel electronics from suppressed-freezing tuned polymer amorphization. Nat. Commun. 14, 5010 (2023).

    Article  Google Scholar 

  304. Adu-Berchie, K. et al. Adoptive T cell transfer and host antigen-presenting cell recruitment with cryogel scaffolds promotes long-term protection against solid tumors. Nat. Commun. 14, 3546 (2023).

    Article  Google Scholar 

  305. Bencherif, S. A. et al. Injectable cryogel-based whole-cell cancer vaccines. Nat. Commun. 6, 7556 (2015).

    Article  Google Scholar 

  306. Shi, J. et al. Active biointegrated living electronics for managing inflammation. Science 384, 1023–1030 (2024).

    Article  Google Scholar 

  307. Li, P., Kim, S. & Tian, B. Beyond 25 years of biomedical innovation in nano-bioelectronics. Device 2, 100401 (2024).

    Article  Google Scholar 

  308. Chen, G., Li, Y., Bick, M. & Chen, J. Smart textiles for electricity generation. Chem. Rev. 120, 3668–3720 (2020).

    Article  Google Scholar 

  309. Yao, Z. et al. Virtual elastography ultrasound via generative adversarial network for breast cancer diagnosis. Nat. Commun. 14, 788 (2023).

    Article  Google Scholar 

  310. Davoodi, E. et al. Imaging-guided deep tissue in vivo sound printing. Science 388, 616–623 (2025). This article reports a technique that applies focused ultrasound to 3D-printed biomaterials inside living tissues.

    Article  Google Scholar 

  311. Kuo, S. C. & Sheetz, M. P. Force of single kinesin molecules measured with optical tweezers. Science 260, 232–234 (1993).

    Article  Google Scholar 

  312. Weinbaum, S., Cowin, S. C. & Zeng, Y. A model for the excitation of osteocytes by mechanical loading-induced bone fluid shear stresses. J. Biomech. 27, 339–360 (1994).

    Article  Google Scholar 

  313. Frangos, J. A., Eskin, S. G., McIntire, L. V. & Ives, C. L. Flow effects on prostacyclin production by cultured human endothelial cells. Science 227, 1477–1479 (1985).

    Article  Google Scholar 

  314. Olesen, S.-P., Claphamt, D. & Davies, P. Haemodynamic shear stress activates a K+ current in vascular endothelial cells. Nature 331, 168–170 (1988).

    Article  Google Scholar 

  315. Li, S. et al. Fluid shear stress activation of focal adhesion kinase: linking to mitogen-activated protein kinases. J. Biol. Chem. 272, 30455–30462 (1997).

    Article  Google Scholar 

  316. Ingber, D. E. Tensegrity: the architectural basis of cellular mechanotransduction. Annu. Rev. Physiol. 59, 575–599 (1997).

    Article  Google Scholar 

  317. Chen, C. S., Mrksich, M., Huang, S., Whitesides, G. M. & Ingber, D. E. Geometric control of cell life and death. Science 276, 1425–1428 (1997).

    Article  Google Scholar 

  318. Curtis, A. & Wilkinson, C. Topographical control of cells. Biomaterials 18, 1573–1583 (1997).

    Article  Google Scholar 

  319. Dupont, S. et al. Role of yap/taz in mechanotransduction. Nature 474, 179–183 (2011).

    Article  Google Scholar 

  320. Krammer, A., Craig, D., Thomas, W. E., Schulten, K. & Vogel, V. A structural model for force regulated integrin binding to fibronectin’s RGD-synergy site. Matrix Biol. 21, 139–147 (2002).

    Article  Google Scholar 

  321. Kechagia, J. Z., Ivaska, J. & Roca-Cusachs, P. Integrins as biomechanical sensors of the microenvironment. Nat. Rev. Mol. Cell Biol. 20, 457–473 (2019).

    Article  Google Scholar 

  322. Wang, N., Butler, J. P. & Ingber, D. E. Mechanotransduction across the cell surface and through the cytoskeleton. Science 260, 1124–1127 (1993).

    Article  Google Scholar 

  323. Choquet, D., Felsenfeld, D. P. & Sheetz, M. P. Extracellular matrix rigidity causes strengthening of integrin–cytoskeleton linkages. Cell 88, 39–48 (1997).

    Article  Google Scholar 

  324. Saotome, K. et al. Structure of the mechanically activated ion channel piezo1. Nature 554, 481–486 (2018).

    Article  Google Scholar 

  325. Elosegui-Artola, A. et al. Mechanical regulation of a molecular clutch defines force transmission and transduction in response to matrix rigidity. Nat. Cell Biol. 18, 540–548 (2016).

    Article  Google Scholar 

  326. Kong, F., García, A. J., Mould, A. P., Humphries, M. J. & Zhu, C. Demonstration of catch bonds between an integrin and its ligand. J. Cell Biol. 185, 1275–1284 (2009).

    Article  Google Scholar 

  327. Salatino, J. W., Ludwig, K. A., Kozai, T. D. Y. & Purcell, E. K. Glial responses to implanted electrodes in the brain. Nat. Biomed. Eng. 1, 862–877 (2017).

    Article  Google Scholar 

Download references