Cell contraction induces long-ranged stress stiffening in the extracellular matrix

Yu Long Han, Pierre Ronceray, Guoqiang Xu, Andrea Malandrino, Roger D. Kamm, Martin Lenz, Chase P. Broedersz, Ming Guo

Research output: Contribution to JournalArticleAcademicpeer-review

Abstract

Animal cells in tissues are supported by biopolymer matrices, which typically exhibit highly nonlinear mechanical properties. While the linear elasticity of the matrix can significantly impact cell mechanics and functionality, it remains largely unknown how cells, in turn, affect the nonlinear mechanics of their surrounding matrix. Here, we show that living contractile cells are able to generate a massive stiffness gradient in three distinct 3D extracellular matrix model systems: collagen, fibrin, and Matrigel. We decipher this remarkable behavior by introducing nonlinear stress inference microscopy (NSIM), a technique to infer stress fields in a 3D matrix from nonlinear microrheology measurements with optical tweezers. Using NSIM and simulations, we reveal large long-ranged cell-generated stresses capable of buckling filaments in the matrix. These stresses give rise to the large spatial extent of the observed cell-induced matrix stiffness gradient, which can provide a mechanism for mechanical communication between cells.
Original languageEnglish
Pages (from-to)4075-4080
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume115
Issue number16
DOIs
Publication statusPublished - 17 Apr 2018
Externally publishedYes

Funding

We thank Anna Posfai for useful comments. This work was supported by National Cancer Institute Grant 1U01CA202123 (to M.G.), the German Excellence Initiative via the program “NanoSystems Initiative Munich” (to C.P.B.) and DFG via project B12 within the SFB-1032 (to C.P.B.), a Princeton Center for Theoretical Science fellowship (to P.R.), and a Massachusetts Institute of Technology International Science and Technology Initiatives-Germany seed fund (to M.G. and C.P.B.). M.G. also acknowledges support from the Department of Mechanical Engineering at Massachusetts Institute of Technology. A.M. is supported by European Union's Seventh Framework Programme for Research Grant 625500. M.L. was supported by Marie Curie Integration Grant PCIG12-GA-2012-334053, “Investissements d'Avenir” LabEx PALM Grant ANR-10-LABX-0039-PALM, Agence Nationale de la Recherche Grant ANR-15-CE13-0004-03, and European Research Council Starting Grant 677532. M.L.'s group belongs to the CNRS consortium CellTiss. This work was performed in part at the Aspen Center for Physics, which is supported by National Science Foundation Grant PHY-1607611. ACKNOWLEDGMENTS. We thank Anna Posfai for useful comments. This work was supported by National Cancer Institute Grant 1U01CA202123 (to M.G.), the German Excellence Initiative via the program “NanoSystems Initiative Munich” (to C.P.B.) and DFG via project B12 within the SFB-1032 (to C.P.B.), a Princeton Center for Theoretical Science fellowship (to P.R.), and a Massachusetts Institute of Technology International Science and Technology Initiatives–Germany seed fund (to M.G. and C.P.B.). M.G. also acknowledges support from the Department of Mechanical Engineering at Massachusetts Institute of Technology. A.M. is supported by European Union’s Seventh Framework Programme for Research Grant 625500. M.L. was supported by Marie Curie Integration Grant PCIG12-GA-2012-334053, “Investissements d’Avenir” LabEx PALM Grant ANR-10-LABX-0039-PALM, Agence Nationale de la Recherche Grant ANR-15-CE13-0004-03, and European Research Council Starting Grant 677532. M.L.’s group belongs to the CNRS consortium CellTiss. This work was performed in part at the Aspen Center for Physics, which is supported by National Science Foundation Grant PHY-1607611.

FundersFunder number
Department of Mechanical Engineering at Massachusetts Institute of Technology
German Excellence Initiative
Princeton Center for Theoretical Science
National Science FoundationPHY-1607611
National Cancer InstituteU01CA202123
Office of Legacy Management
Massachusetts Institute of Technology
Department of Mechanical Engineering, College of Engineering, Michigan State University
European Research Council677532
Deutsche ForschungsgemeinschaftSFB-1032
Agence Nationale de la RechercheANR-15-CE13-0004-03
Seventh Framework ProgrammePCIG12-GA-2012-334053, 625500, ANR-10-LABX-0039-PALM

    Keywords

    • Biopolymer networks
    • Cell mechanics
    • Cell-matrix interactions
    • Microrheology
    • Nonlinear elasticity

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