Cell contraction induces long-ranged stress stiffening in the extracellular matrix

TL;DR

This study demonstrates that contractile cells can induce extensive, long-range stiffening in 3D extracellular matrices through stress propagation caused by filament buckling, revealing a potential mechanism for cellular communication.

Contribution

The paper introduces Nonlinear Stress Inference Microscopy (NSIM) to map stress fields in 3D matrices and uncovers how cell-generated stresses propagate over long distances, causing matrix stiffening.

Findings

Cells generate a large stiffness gradient in 3D matrices.

Stress propagates over long distances due to filament buckling.

Cell-induced stress gradients may facilitate mechanical communication.

Abstract

Animal cells in tissues are supported by biopolymer matrices, which typically exhibit highly nonlinear mechanical properties. While the linear elasticity of the matrix can significantly impact cell mechanics and functionality, it remains largely unknown how cells, in turn, affect the nonlinear mechanics of their surrounding matrix. Here we show that living contractile cells are able to generate a massive stiffness gradient in three distinct 3D extracellular matrix model systems: collagen, fibrin, and Matrigel. We decipher this remarkable behavior by introducing Nonlinear Stress Inference Microscopy (NSIM), a novel technique to infer stress fields in a 3D matrix from nonlinear microrheology measurement with optical tweezers. Using NSIM and simulations, we reveal a long-ranged propagation of cell-generated stresses resulting from local filament buckling. This slow decay of stress gives rise to the large spatial extent of the observed cell-induced matrix stiffness gradient, which could form a mechanism for mechanical communication between cells.