Computational modeling of three-dimensional ECM-rigidity sensing to guide directed cell migration
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E390.full.pdf
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Author(s)
Silberberg, Yaron R.
Kim, Min-Cheol
Abeyaratne, Rohan
Kamm, Roger Dale
Asada, Haruhiko
Date Issued
January 2018
Journal
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences (U.S.)
Citation
Kim, Min-Cheol et al. “Computational Modeling of Three-Dimensional ECM-Rigidity Sensing to Guide Directed Cell Migration.” Proceedings of the National Academy of Sciences 115, 3 (January 2, 2018): E390–E399 © 2018 National Academy of Sciences
Version
Final published version
Abstract
Filopodia have a key role in sensing both chemical and mechanical cues in surrounding extracellular matrix (ECM). However, quantitative understanding is still missing in the filopodialmechanosensing of local ECM stiffness, resulting from dynamic interactions between filopodia and the surrounding 3D ECM fibers. Here we present a method for characterizing the stiffness of ECM that is sensed by filopodia based on the theory of elasticity and discrete ECM fiber. We have applied this method to a filopodial mechanosensing model for predicting directed cell migration toward stiffer ECM. This model provides us with a distribution of force and displacement as well as their time rate of changes near the tip of a filopodium when it is bound to the surrounding ECM fibers. Aggregating these effects in each local region of 3D ECM, we express the local ECM stiffness sensed by the cell and explain polarity in the cellular durotaxis mechanism. Keywords: filopodia; mechanosensing; ECM; durotaxis; computational modeling
MIT Department
Massachusetts Institute of Technology. Department of Biological Engineering
Massachusetts Institute of Technology. Department of Mechanical Engineering
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Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
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DOI of Published Version
https://doi.org/10.1073/PNAS.1717230115
