Dynamic filopodial forces induce accumulation, damage, and plastic remodeling of 3D extracellular matrices
Name
journal.pcbi.1006684.pdf
Description
Published version
Size
3.48 MB
Format
Adobe PDF
Checksum (MD5)
7b6eb3363c6fefb8488bd221dd262102
Author(s)
Malandrino, Andrea
Kamm, Roger D.
Date Issued
April 8, 2019
Journal
PloS one
Publisher
Public Library of Science (PLoS)
Citation
Malandrino, Andrea er al. "Dynamic filopodial forces induce accumulation, damage, and plastic remodeling of 3D extracellular matrices." PloS one 15 (2019): e1006684 © 2019 The Author(s)
Version
Final published version
Abstract
The mechanical properties of the extracellular matrix (ECM)–a complex, 3D, fibrillar scaffold of cells in physiological environments–modulate cell behavior and can drive tissue morphogenesis, regeneration, and disease progression. For simplicity, it is often convenient to assume these properties to be time-invariant. In living systems, however, cells dynamically remodel the ECM and create time-dependent local microenvironments. Here, we show how cell-generated contractile forces produce substantial irreversible changes to the density and architecture of physiologically relevant ECMs–collagen I and fibrin–in a matter of minutes. We measure the 3D deformation profiles of the ECM surrounding cancer and endothelial cells during stages when force generation is active or inactive. We further correlate these ECM measurements to both discrete fiber simulations that incorporate fiber crosslink unbinding kinetics and continuum-scale simulations that account for viscoplastic and damage features. Our findings further confirm that plasticity, as a mechanical law to capture remodeling in these networks, is fundamentally tied to material damage via force-driven unbinding of fiber crosslinks. These results characterize in a multiscale manner the dynamic nature of the mechanical environment of physiologically mimicking cell-in-gel systems.
Subjects
Ecology
Modelling and Simulation
Computational Theory and Mathematics
Genetics
Ecology, Evolution, Behavior and Systematics
Molecular Biology
Cellular and Molecular Neuroscience
MIT Department
Massachusetts Institute of Technology. Department of Mechanical Engineering
Massachusetts Institute of Technology. Department of Biological Engineering
Terms of Use
Creative Commons Attribution 4.0 International license
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1371/journal.pcbi.1006684
