Abstract
Nonlinear stiffening is a ubiquitous property of major types of biopolymers that make up the extracellular matrices (ECM) including collagen, fibrin, and basement membrane. Within the ECM, many types of cells such as fibroblasts and cancer cells have a spindle-like shape that acts like two equal and opposite force monopoles, which anisotropically stretch their surroundings and locally stiffen the matrix. Here, we first use optical tweezers to study the nonlinear force-displacement response to localized monopole forces. We then propose an effective-probe scaling argument that a local point force application can induce a stiffened region in the matrix, which can be characterized by a nonlinear length scale R* that increases with the increasing force magnitude; the local nonlinear force-displacement response is a result of the nonlinear growth of this effective probe that linearly deforms an increasing portion of the surrounding matrix. Furthermore, we show that this emerging nonlinear length scale R* can be observed around living cells and can be perturbed by varying matrix concentration or inhibiting cell contractility.
Original language | English |
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Article number | e2304666120 |
Pages (from-to) | 1-7 |
Number of pages | 7 |
Journal | Proceedings of the National Academy of Sciences of the United States of America |
Volume | 120 |
Issue number | 23 |
Early online date | 30 May 2023 |
DOIs | |
Publication status | Published - 6 Jun 2023 |
Funding
ACKNOWLEDGMENTS. We thank R. Abeyaratne, I. Y. Wong, and S. Wasserman for helpful discussions. We would like to acknowledge the support from the NIH (1R01GM140108), MathWorks, and the Jeptha H. and Emily V. Wade Award at the Massachusetts Institute of Technology. H.Y. acknowledges the MathWorks Mechanical Engineering Fellowship. M.G. acknowledges the Sloan Research Fellowship. This project received funding from the European Union’s Horizon 2020 research and innovation program under the Marie Sklodowska-Curie grant agreement no. 891217 and the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation), Project-ID 201269156 - SFB 1032 (Project B12) (E.B. and C.P.B.). P.R. is supported by France 2030, the French National Research Agency (ANR-16-CONV-0001), and the Excellence Initiative of Aix-Marseille University—A*MIDEX.
Funders | Funder number |
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MathWorks Mechanical Engineering Fellowship | |
National Institutes of Health | 1R01GM140108 |
Massachusetts Institute of Technology | |
Aix-Marseille Université | |
Horizon 2020 Framework Programme | 891217 |
Deutsche Forschungsgemeinschaft | 201269156 - SFB 1032 |
Agence Nationale de la Recherche | ANR-16-CONV-0001 |
Keywords
- biopolymer networks
- cell–matrix interactions
- microrheology
- nonlinear elasticity