Mechanical forces from intercellular peptide self-assembly drive spheroid formation

References

Mouw, J. K., Ou, G. & Weaver, V. M. Extracellular matrix assembly: a multiscale deconstruction. Nat. Rev. Mol. Cell Biol. 15, 771–785 (2014).

Google Scholar
Theocharis, A. D., Skandalis, S. S., Gialeli, C. & Karamanos, N. K. Extracellular matrix structure. Adv. Drug Deliv. Rev. 97, 4–27 (2016).

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

Google Scholar
Rosales, A. M. & Anseth, K. S. The design of reversible hydrogels to capture extracellular matrix dynamics. Nat. Rev. Mater. 1, 1–15 (2016).

Google Scholar
Kyriakopoulou, K., Piperigkou, Z., Tzaferi, K. & Karamanos, N. K. Trends in extracellular matrix biology. Mol. Biol. Rep. 50, 853–863 (2023).

Google Scholar
Hynes, R. O. Stretching the boundaries of extracellular matrix research. Nat. Rev. Mol. Cell Biol. 15, 761–763 (2014).

Google Scholar
Geiger, B., Bershadsky, A., Pankov, R. & Yamada, K. M. Transmembrane crosstalk between the extracellular matrix and the cytoskeleton. Nat. Rev. Mol. Cell Biol. 2, 793–805 (2001).

Google Scholar
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).

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

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

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

Google Scholar
del Rio, A. et al. Stretching single talin rod molecules activates vinculin binding. Science 323, 638–641 (2009).

Google Scholar
Aragona, M. et al. A mechanical checkpoint controls multicellular growth through YAP/TAZ regulation by actin-processing factors. Cell 154, 1047–1059 (2013).

Google Scholar
Stowers, R. S. et al. Matrix stiffness induces a tumorigenic phenotype in mammary epithelium through changes in chromatin accessibility. Nat. Biomed. Eng. 3, 1009–1019 (2019).

Google Scholar
Stupack, D. G. & Cheresh, D. A. ECM remodeling regulates angiogenesis: endothelial integrins look for new ligands. Sci. STKE 2002, pe7–pe7 (2002).

Google Scholar
Wade, R. J. & Burdick, J. A. Engineering ECM signals into biomaterials. Mater. Today 15, 454–459 (2012).

Google Scholar
Xu, Y. et al. Convergent synthesis of diversified reversible network leads to liquid metal-containing conductive hydrogel adhesives. Nat. Commun. 12, 2407 (2021).

Google Scholar
Zhu, M. et al. In vivo engineered extracellular matrix scaffolds with instructive niches for oriented tissue regeneration. Nat. Commun. 10, 4620 (2019).

Google Scholar
Ai, S. et al. A SupraGel for efficient production of cell spheroids. Sci. China Mater. 65, 1655–1661 (2022).

Google Scholar
Zhang, Y. et al. Mesenchymal stem cell spheroids induced by supramolecular nanofibers for diabetic wound healing. Adv. Funct. Mater. 34, 2314607 (2024).
Wang, H. et al. An in situ dynamic continuum of supramolecular phosphoglycopeptides enables formation of 3D cell spheroids. Angew. Chem., Int Ed. 56, 16297–16301 (2017).

Google Scholar
Guo, J. et al. Cell spheroid creation by transcytotic intercellular gelation. Nat. Nanotechnol. 18, 1094–1104 (2023).

Google Scholar
Hinderer, S., Layland, S. L. & Schenke-Layland, K. ECM and ECM-like materials—biomaterials for applications in regenerative medicine and cancer therapy. Adv. Drug Deliv. Rev. 97, 260–269 (2016).

Google Scholar
Kyburz, K. A. & Anseth, K. S. Synthetic mimics of the extracellular matrix: how simple is complex enough? Ann. Biomed. Eng. 43, 489–500 (2015).

Google Scholar
Elosegui-Artola, A. The extracellular matrix viscoelasticity as a regulator of cell and tissue dynamics. Curr. Opin. Cell Biol. 72, 10–18 (2021).

Google Scholar
Datta, P., Ayan, B. & Ozbolat, I. T. Bioprinting for vascular and vascularized tissue biofabrication. Acta Biomater. 51, 1–20 (2017).

Google Scholar
Grebenyuk, S. et al. Large-scale perfused tissues via synthetic 3D soft microfluidics. Nat. Commun. 14, 193 (2023).

Google Scholar
Jiang, Y. et al. Targeting extracellular matrix stiffness and mechanotransducers to improve cancer therapy. J. Hematol. Oncol. 15, 34 (2022).

Google Scholar
Yang, X., Lu, H., Tao, Y., Zhou, L. & Wang, H. Spatiotemporal control over chemical assembly in living cells by integration of acid-catalyzed hydrolysis and enzymatic reactions. Angew. Chem. Int. Ed. 60, 23797–23804 (2021).

Google Scholar
Liu, Z., Guo, J., Qiao, Y. & Xu, B. Enzyme-instructed intracellular peptide assemblies. Acc. Chem. Res. 56, 3076–3088 (2023).

Google Scholar
Zhang, Y. et al. Molecular recognition remolds the self-assembly of hydrogelators and increases the elasticity of the hydrogel by 106-fold. J. Am. Chem. Soc. 126, 15028–15029 (2004).

Google Scholar
Ciucurel, E. C. & Sefton, M. V. A poloxamine–polylysine acrylate scaffold for modular tissue engineering. J. Biomater. Sci. Polym. Ed. 22, 2515–2528 (2011).

Google Scholar
Aksenov, M. Y., Aksenova, M. V., Mactutus, C. F. & Booze, R. M. HIV-1 protein-mediated amyloidogenesis in rat hippocampal cell cultures. Neurosci. Lett. 475, 174–178 (2010).

Google Scholar
Millán J. L. Mammalian Alkaline Phosphatases: From Biology to Applications in Medicine and Biotechnology (Wiley, 2006).
Fedde, K. N., Lane, C. C. & Whyte, M. P. Alkaline phosphatase is an ectoenzyme that acts on micromolar concentrations of natural substrates at physiologic pH in human osteosarcoma (SAOS-2) cells. Arch. Biochem. Biophys. 264, 400–409 (1988).

Google Scholar
Zhou, J. et al. Enzyme-instructed self-assembly for spatiotemporal profiling of the activities of alkaline phosphatases on live cells. Chem 1, 246–263 (2016).

Google Scholar
Nicolas, J. et al. 3D extracellular matrix mimics: fundamental concepts and role of materials chemistry to influence stem cell fate. Biomacromolecules 21, 1968–1994 (2020).

Google Scholar
Cukierman, E., Pankov, R., Stevens, D. R. & Yamada, K. M. Taking cell-matrix adhesions to the third dimension. Science 294, 1708–1712 (2001).

Google Scholar
Craig, S. W. & Chen, H. Lamellipodia protrusion: moving interactions of vinculin and Arp2/3. Curr. Biol. 13, R236–R238 (2003).

Google Scholar
Spector, I., Shochet, N. R., Kashman, Y. & Groweiss, A. Latrunculins: novel marine toxins that disrupt microfilament organization in cultured cells. Science 219, 493–495 (1983).

Google Scholar
Hetrick, B., Han, M. inS., Helgeson, L. ukeA. & Nolen, B. radJ. Small molecules CK-666 and CK-869 inhibit actin-related protein 2/3 complex by blocking an activating conformational change. Chem. Biol. 20, 701–712 (2013).

Google Scholar
Dupont, S. et al. Role of YAP/TAZ in mechanotransduction. Nature 474, 179–183 (2011).

Google Scholar
Kandasamy, S. et al. The YAP1 signaling inhibitors, verteporfin and CA3, suppress the mesothelioma cancer stem cell phenotype. Mol. Cancer Res. 18, 343–351 (2020).

Google Scholar
Auger, F. A., Gibot, L. & Lacroix, D. The pivotal role of vascularization in tissue engineering. Annu. Rev. Biomed. Eng. 15, 177–200 (2013).

Google Scholar
Laschke, M. W. et al. Angiogenesis in tissue engineering: breathing life into constructed tissue substitutes. Tissue Eng. 12, 2093–2104 (2006).

Google Scholar
Shirure, V. S., Hughes, C. C. W. & George, S. C. Engineering vascularized organoid-on-a-chip models. Annu Rev. Biomed. Eng. 23, 141–167 (2021).

Google Scholar
Bieker, R. et al. Infarction of tumor vessels by NGR-peptide–directed targeting of tissue factor: experimental results and first-in-man experience. Blood 113, 5019–5027 (2009).

Google Scholar
Wang, X. et al. NGR-modified micelles enhance their interaction with CD13-overexpressing tumor and endothelial cells. J. Controlled Release 139, 56–62 (2009).

Google Scholar
Walter-Yohrling, J., Pratt, B. M., Ledbetter, S. & Teicher, B. A. Myofibroblasts enable invasion of endothelial cells into three-dimensional tumor cell clusters: a novel in vitro tumor model. Cancer Chemother. Pharm. 52, 263–269 (2003).

Google Scholar
Ehsan, S. M., Welch-Reardon, K. M., Waterman, M. L., Hughes, C. C. W. & George, S. C. A three-dimensional in vitro model of tumor cell intravasation. Integr. Biol. 6, 603–610 (2014).

Google Scholar
Batlle, R. et al. Regulation of tumor angiogenesis and mesenchymal–endothelial transition by p38α through TGF-β and JNK signaling. Nat. Commun. 10, 3071 (2019).

Google Scholar
Sokolova, V. et al. Transport of ultrasmall gold nanoparticles (2 nm) across the blood–brain barrier in a six-cell brain spheroid model. Sci. Rep. 10, 18033 (2020).

Google Scholar
Zheng, Y. et al. In vitro microvessels for the study of angiogenesis and thrombosis. Proc. Natl. Acad. Sci. 109, 9342–9347 (2012).

Google Scholar
Henrik Heiland, D. et al. Tumor-associated reactive astrocytes aid the evolution of immunosuppressive environment in glioblastoma. Nat. Commun. 10, 2541 (2019).

Google Scholar
Benton, G., Arnaoutova, I., George, J., Kleinman, H. K. & Koblinski, J. Matrigel: from discovery and ECM mimicry to assays and models for cancer research. Adv. Drug Deliv. Rev. 79-80, 3–18 (2014).

Google Scholar
Yang, J. et al. Bioengineering and vascularization strategies for islet organoids: advancing toward diabetes therapy. Metabolism 152, 155786 (2024).

Google Scholar

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