article · 01/05/2012
Evidence of a large-scale mechanosensing mechanism for cellular adaptation to substrate stiffness
Résumé
Cell migration plays a major role in many fundamental biological processes, such as morphogenesis, tumor metastasis, and wound healing. As they anchor and pull on their surroundings, adhering cells actively probe the stiffness of their environment. Current understanding is that traction forces exerted by cells arise mainly at mechanotransduction sites, called focal adhesions, whose size seems to be correlated to the force exerted by cells on their underlying substrate, at least during their initial stages. In fact, our data show by direct measurements that the buildup of traction forces is faster for larger substrate stiffness, and that the stress measured at adhesion sites depends on substrate rigidity. Our results, backed by a phenomenological model based on active gel theory, suggest that rigidity-sensing is mediated by a large-scale mechanism originating in the cytoskeleton instead of a local one. We show that large-scale mechanosensing leads to an adaptative response of cell migration to stiffness gradients. In response to a step boundary in rigidity, we observe not only that cells migrate preferentially toward stiffer substrates, but also that this response is optimal in a narrow range of rigidities. Taken together, these findings lead to unique insights into the regulation of cell response to external mechanical cues and provide evidence for a cytoskeleton-based rigidity-sensing mechanism.
Citer cet article
Trichet, L., Le Digabel, J., Hawkins, R.-J., Vedula, R.-K., Gupta, M., Ribrault, C., Hersen, P., Voituriez, R., & Ladoux, B. (2012). Evidence of a large-scale mechanosensing mechanism for cellular adaptation to substrate stiffness. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 109(18). https://doi.org/10.1073/pnas.1117810109@article{Trichet2012_249,
author = {Trichet, Lea and Le Digabel, Jimmy and Hawkins, Rhoda J. and Vedula, Ram Krishna and Gupta, Mukund and Ribrault, Claire and Hersen, Pascal and Voituriez, Raphael and Ladoux, Benoit},
year = {2012},
month = {5},
title = {Evidence of a large-scale mechanosensing mechanism for cellular adaptation to substrate stiffness},
journal = {PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA},
volume = {109},
number = {18},
abstract = {Cell migration plays a major role in many fundamental biological processes, such as morphogenesis, tumor metastasis, and wound healing. As they anchor and pull on their surroundings, adhering cells actively probe the stiffness of their environment. Current understanding is that traction forces exerted by cells arise mainly at mechanotransduction sites, called focal adhesions, whose size seems to be correlated to the force exerted by cells on their underlying substrate, at least during their initial stages. In fact, our data show by direct measurements that the buildup of traction forces is faster for larger substrate stiffness, and that the stress measured at adhesion sites depends on substrate rigidity. Our results, backed by a phenomenological model based on active gel theory, suggest that rigidity-sensing is mediated by a large-scale mechanism originating in the cytoskeleton instead of a local one. We show that large-scale mechanosensing leads to an adaptative response of cell migration to stiffness gradients. In response to a step boundary in rigidity, we observe not only that cells migrate preferentially toward stiffer substrates, but also that this response is optimal in a narrow range of rigidities. Taken together, these findings lead to unique insights into the regulation of cell response to external mechanical cues and provide evidence for a cytoskeleton-based rigidity-sensing mechanism.},
url = {http://www.dx.doi.org/10.1073/pnas.1117810109},
doi = {10.1073/pnas.1117810109},
issn = {0027-8424},
}TY - JOUR
AU - Trichet, Lea
AU - Le Digabel, Jimmy
AU - Hawkins, Rhoda J.
AU - Vedula, Ram Krishna
AU - Gupta, Mukund
AU - Ribrault, Claire
AU - Hersen, Pascal
AU - Voituriez, Raphael
AU - Ladoux, Benoit
PY - 2012
DA - 2012/05/01
TI - Evidence of a large-scale mechanosensing mechanism for cellular adaptation to substrate stiffness
JO - PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
VL - 109
IS - 18
SN - 0027-8424
AB - Cell migration plays a major role in many fundamental biological processes, such as morphogenesis, tumor metastasis, and wound healing. As they anchor and pull on their surroundings, adhering cells actively probe the stiffness of their environment. Current understanding is that traction forces exerted by cells arise mainly at mechanotransduction sites, called focal adhesions, whose size seems to be correlated to the force exerted by cells on their underlying substrate, at least during their initial stages. In fact, our data show by direct measurements that the buildup of traction forces is faster for larger substrate stiffness, and that the stress measured at adhesion sites depends on substrate rigidity. Our results, backed by a phenomenological model based on active gel theory, suggest that rigidity-sensing is mediated by a large-scale mechanism originating in the cytoskeleton instead of a local one. We show that large-scale mechanosensing leads to an adaptative response of cell migration to stiffness gradients. In response to a step boundary in rigidity, we observe not only that cells migrate preferentially toward stiffer substrates, but also that this response is optimal in a narrow range of rigidities. Taken together, these findings lead to unique insights into the regulation of cell response to external mechanical cues and provide evidence for a cytoskeleton-based rigidity-sensing mechanism.
DO - 10.1073/pnas.1117810109
UR - http://www.dx.doi.org/10.1073/pnas.1117810109
ER -