A computational framework for modeling cell-matrix interactions in soft biological tissues

TL;DR

This paper introduces a finite element computational framework that models cell-matrix interactions at the microscale to better understand the mechanisms behind mechanical homeostasis in soft tissues.

Contribution

It presents a novel bottom-up modeling approach incorporating cellular mechanobiological mechanisms within a 3D extracellular matrix.

Findings

Reproduces experimental observations of mechanical homeostasis over short time scales

Models key cellular mechanisms like actin contraction and molecular clutch behavior

Provides a systematic tool for future in silico studies of tissue mechanics

Abstract

Living soft tissues appear to promote the development and maintenance of a preferred mechanical state within a defined tolerance around a so-called set-point. This phenomenon is often referred to as mechanical homeostasis. In contradiction to the prominent role of mechanical homeostasis in various (patho)physiological processes, its underlying micromechanical mechanisms acting on the level of individual cells and fibers remain poorly understood, especially, how these mechanisms on the microscale lead to what we macroscopically call mechanical homeostasis. Here, we present a novel finite element based computational framework that is constructed bottom up, that is, it models key mechanobiological mechanisms such as actin cytoskeleton contraction and molecular clutch behavior of individual cells interacting with a reconstructed three-dimensional extracellular fiber matrix. The framework reproduces many experimental observations regarding mechanical homeostasis on short time scales (hours), in which the deposition and degradation of extracellular matrix can largely be neglected. This model can serve as a systematic tool for future in silico studies of the origin of the numerous still unexplained experimental observations about mechanical homeostasis.