Cell contractility facilitates alignment of cells and tissues to static uniaxial stretch

TL;DR

This study uses a computational model to show how cell contractility enhances alignment and string formation of cells and tissues in response to static uniaxial stretch, mimicking developmental and homeostatic processes.

Contribution

It introduces a hybrid cellular Potts and finite-element model demonstrating the role of active cell contractility in tissue alignment under mechanical stretch, aligning with experimental observations.

Findings

Active contractility accelerates cell reorientation to stretch.

Cells form string-like structures aligned with stretch.

Stretch magnitude and contractile force influence pattern formation.

Abstract

During animal development and homeostasis, the structure of tissues, including muscles, blood vessels and connective tissues adapts to mechanical strains in the extracellular matrix (ECM). These strains originate from the differential growth of tissues or forces due to muscle contraction or gravity. Here we show using a computational model that by amplifying local strain cues, active cell contractility can facilitate and accelerate the reorientation of single cells to static strains. At the collective cell level, the model simulations show that active cell contractility can facilitate the formation of strings along the orientation of stretch. The computational model is based on a hybrid cellular Potts and finite-element simulation framework describing a mechanical cell-substrate feedback, where: 1) cells apply forces on the ECM, such that 2) local strains are generated in the ECM, and 3) cells preferentially extend protrusions along the strain orientation. In accordance with experimental observations, simulated cells align and form string-like structures parallel to static uniaxial stretch. Our model simulations predict that the magnitude of the uniaxial stretch and the strength of the contractile forces regulate a gradual transition between string-like patterns and vascular network-like patterns. Our simulations also suggest that at high population densities, less cell cohesion promotes string formation.