Cell Shape and Durotaxis Explained from Cell-Extracellular Matrix Forces and Focal Adhesion Dynamics.

Elisabeth G Rens,Roeland M.H Merks

doi:10.1016/j.isci.2020.101488

Elisabeth G Rens, Roeland M.H Merks

Open Access

https://doi.org/10.1016/j.isci.2020.101488

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Abstract

SummaryMany cells are small and rounded on soft extracellular matrices (ECM), elongated on stiffer ECMs, and flattened on hard ECMs. Cells also migrate up stiffness gradients (durotaxis). Using a hybrid cellular Potts and finite-element model extended with ODE-based models of focal adhesion (FA) turnover, we show that the full range of cell shape and durotaxis can be explained in unison from dynamics of FAs, in contrast to previous mathematical models. In our 2D cell-shape model, FAs grow due to cell traction forces. Forces develop faster on stiff ECMs, causing FAs to stabilize and, consequently, cells to spread on stiff ECMs. If ECM stress further stabilizes FAs, cells elongate on substrates of intermediate stiffness. We show that durotaxis follows from the same set of assumptions. Our model contributes to the understanding of the basic responses of cells to ECM stiffness, paving the way for future modeling of more complex cell-ECM interactions.

Highlights

Mechanical interactions between cells and the extracellular matrix (ECM) are crucial for the formation and function of tissues
Using a hybrid cellular Potts and finite-element model extended with ordinary differential equations (ODEs)-based models of focal adhesion (FA) turnover, we show that the full range of cell shape and durotaxis can be explained in unison from dynamics of FAs, in contrast to previous mathematical models
In our 2D cell-shape model, FAs grow due to cell traction forces

Summary

Introduction

Mechanical interactions between cells and the extracellular matrix (ECM) are crucial for the formation and function of tissues. On highly rigid substrates such as glass, cells spread out and flatten This behavior has been observed for a wide range of cell types, including endothelial cells (Califano and Reinhart-King, 2010), fibroblasts (Ghibaudo et al, 2008; Pelham and Wang, 1997; Prager-Khoutorsky et al, 2011), smooth muscle cells (Engler et al, 2004), and osteogenic cells (Mullen et al, 2015). Cells tend to migrate toward stiffer parts of the ECM, a phenomenon known as durotaxis Such behavior occurs for a wide range of mammalian cell types, including fibroblasts (Lo et al, 2000), vascular smooth muscle cells (Isenberg et al, 2009), mesenchymal stem cells (Vincent et al, 2013), and neurons and glioma cells (Bangasser et al, 2017). We show that a single model suffices to explain (a) increased cell area on stiffer substrates, (b) cell elongation on substrates of intermediate stiffness, and (c) durotaxis

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