Modeling the Mechanosensitivity of Fast-Crawling Cells on Cyclically Stretched Substrates

TL;DR

This paper presents a computational model explaining how fast-crawling cells reorient on cyclically stretched substrates, highlighting the role of focal adhesion dynamics and asymmetries in the stretching protocol.

Contribution

The study introduces a novel computational model linking sub-cellular processes to cell reorientation under cyclic stretch, emphasizing focal adhesion dynamics and asymmetry effects.

Findings

Reorientation depends strongly on stretching frequency.

Asymmetry in loading/unloading phases influences cell alignment direction.

Model matches experimental observations of cell behavior.

Abstract

The mechanosensitivity of cells, which determines how they are able to respond to mechanical signals received from their environment, is crucial for the functioning of all biological systems. In experiments, cells placed on cyclically stretched substrates have been shown to reorient in a direction that depends not only on the type of cell, but also on the mechanical properties of the substrate, and the amplitude and rate of stretching. However, the underlying biochemical and mechanical mechanisms responsible for this realignment are still not completely understood. In this study, we introduce a computational model for fast crawling on cyclically stretched substrates that accounts for the sub-cellular processes responsible for the cell shape and motility, as well as the coupling to the substrate through the focal adhesion sites. In particular, we focus on the role of the focal adhesion dynamics, and show that the reorientation under cyclic stretching is strongly dependent on the frequency, as has been observed experimentally. Furthermore, we show that an asymmetry during the loading and unloading phases of the stretching, whether coming from the response of the cell itself, or from the stretching protocol, can be used to selectively align the cells in either the parallel or perpendicular directions.