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Cells exploit a phase transition to mechanically remodel the fibrous extracellular matrix

Grekas, Georgios and Proestaki, Maria and Rosakis, Phoebus and Notbohm, Jacob and Makridakis, Charalambos and Ravichandran, Guruswami (2021) Cells exploit a phase transition to mechanically remodel the fibrous extracellular matrix. Journal of the Royal Society Interface, 18 (175). Art. No. 20200823. ISSN 1742-5689.

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Through mechanical forces, biological cells remodel the surrounding collagen network, generating striking deformation patterns. Tethers—tracts of high densification and fibre alignment—form between cells, thinner bands emanate from cell clusters. While tethers facilitate cell migration and communication, how they form is unclear. Combining modelling, simulation and experiment, we show that tether formation is a densification phase transition of the extracellular matrix, caused by buckling instability of network fibres under cell-induced compression, featuring unexpected similarities with martensitic microstructures. Multiscale averaging yields a two-phase, bistable continuum energy landscape for fibrous collagen, with a densified/aligned second phase. Simulations predict strain discontinuities between the undensified and densified phase, which localizes within tethers as experimentally observed. In our experiments, active particles induce similar localized patterns as cells. This shows how cells exploit an instability to mechanically remodel the extracellular matrix simply by contracting, thereby facilitating mechanosensing, invasion and metastasis.

Item Type:Article
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URLURL TypeDescription Paper ItemData Material
Grekas, Georgios0000-0002-0267-0150
Rosakis, Phoebus0000-0002-0383-0961
Ravichandran, Guruswami0000-0002-2912-0001
Alternate Title:Cells exploit a phase transition to establish interconnections in fibrous extracellular matrices
Additional Information:© 2021 The Author(s). Published by the Royal Society. Manuscript received 12/10/2021; Manuscript accepted 27/01/2021; Published online 17/02/2021. We thank Brian Burkel for assistance with microscopy. The work of P.R., C.M. and G.G. was partially supported by the EU Horizon 2020 Research and Innovation Programme under the Marie Sklodowska-Curie project ModCompShock ( agreement no. 642768. The research of G.G. was also supported by a Vannevar Bush Faculty Fellowship. The work of J.N. and M.P. and was partially supported by National Science Foundationgrant number CMMI-1749400. G.R. acknowledges the support of the National Science Foundation (DMR no. 0520565) through the Center for Science and Engineering of Materials at the California Institute of Technology. Data accessibility: The numerical code used in the simulations reported herein is available at Experimental data are available at Authors' contributions: P.R., G.R. and J.N. planned the research. G.G. and P.R. developed the model. G.G. and C.M. developed the numerical method. G.G. performed the simulations. M.P. and J.N. designed the experiments. M.P. performed the experiments; M.P. and J.N. analysed the data. All authors discussed and analysed the results and contributed to writing the manuscript. We declare we have no competing interests.
Funding AgencyGrant Number
Marie Curie Fellowship642768
Vannevar Bush FellowshipUNSPECIFIED
Subject Keywords:ECM remodelling, fibre buckling, phase transition, densification patterns, fibre alignment, tumour biomarkers
Issue or Number:175
Record Number:CaltechAUTHORS:20200122-131403095
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Official Citation:Grekas G, Proestaki M, Rosakis P, Notbohm J, Makridakis C, Ravichandran G. 2021 Cells exploit a phase transition to mechanically remodel the fibrous extracellular matrix. J. R. Soc. Interface 18: 20200823.
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:100843
Deposited By: Tony Diaz
Deposited On:22 Jan 2020 23:16
Last Modified:23 Feb 2021 17:55

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