Cell organization in soft media due to active mechanosensing

TL;DR

This paper presents a unifying model explaining how cells actively sense and respond to the mechanical properties of their environment, aligning their organization with stiffness cues to optimize force application and interaction.

Contribution

It introduces a theoretical framework based on elasticity theory that predicts cell orientation and interaction patterns, aligning well with experimental observations across different conditions.

Findings

Cells orient in the direction of external tensile strain.

Cells align parallel and normal to free and clamped surfaces.

Cells form elastic strings through interactions.

Abstract

Adhering cells actively probe the mechanical properties of their environment and use the resulting information to position and orient themselves. We show that a large body of experimental observations can be consistently explained from one unifying principle, namely that cells strengthen contacts and cytoskeleton in the direction of large effective stiffness. Using linear elasticity theory to model the extracellular environment, we calculate optimal cell organization for several situations of interest and find excellent agreement with experiments for fibroblasts, both on elastic substrates and in collagen gels: cells orient in the direction of external tensile strain, they orient parallel and normal to free and clamped surfaces, respectively, and they interact elastically to form strings. Our method can be applied for rational design of tissue equivalents. Moreover our results indicate that the concept of contact guidance has to be reevaluated. We also suggest that cell-matrix contacts are upregulated by large effective stiffness in the environment because in this way, build-up of force is more efficient.