CUED Publications database

An Integrated Stochastic Model of Matrix-Stiffness-Dependent Filopodial Dynamics

Cheng, B and Lin, M and Li, Y and Huang, G and Yang, H and Genin, GM and Deshpande, VS and Lu, TJ and Xu, F (2016) An Integrated Stochastic Model of Matrix-Stiffness-Dependent Filopodial Dynamics. Biophysical Journal, 111. pp. 2051-2061. ISSN 0006-3495

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© 2016 Biophysical Society The ways that living cells regulate their behavior in response to their local mechanical environment underlie growth, development, and healing and are important to critical pathologies such as metastasis and fibrosis. Although extensive experimental evidence supports the hypothesis that this regulation is governed by the dependence of filopodial dynamics upon extracellular matrix stiffness, the pathways for this dependence are unclear. We therefore developed a model to relate filopodial focal adhesion dynamics to integrin-mediated Rho signaling kinetics. Results showed that focal adhesion maturation, i.e., focal adhesion links reinforcement and integrin clustering, dominates over filopodial dynamics. Downregulated focal adhesion maturation leads to the biphasic relationship between extracellular matrix stiffness and retrograde flow that has been observed in embryonic chick forebrain neurons, whereas upregulated maturation leads to the monotonically decreasing relationship that has been observed in mouse embryonic fibroblasts. When integrin-mediated Rho activation and stress-dependent focal adhesion maturation are combined, the model shows how filopodial dynamics endows cells with exquisite mechanosensing. Taken together, the results support the hypothesis that mechanical and structural factors combine with signaling kinetics to enable cells to probe their environments via filopodial dynamics.

Item Type: Article
Uncontrolled Keywords: Actin Cytoskeleton Animals Biomechanical Phenomena Focal Adhesions Mechanical Phenomena Mice Models, Biological Movement Pseudopodia Stochastic Processes
Divisions: Div C > Materials Engineering
Depositing User: Cron Job
Date Deposited: 17 Jul 2017 19:11
Last Modified: 17 Sep 2020 02:24
DOI: 10.1016/j.bpj.2016.09.026