Local Nonlinear Elastic Response of Extracellular Matrices

TL;DR

This study investigates the local nonlinear elastic response of extracellular matrices using optical tweezers, revealing that local stiffening is weaker than bulk responses and can be modeled as an expanding stiffened region acting as an effective probe.

Contribution

It provides the first characterization of local nonlinear elastic responses in ECM, demonstrating weaker local stiffening and modeling it as an expanding stiffened region.

Findings

Local stiffening responses are significantly weaker than bulk rheology.

A minimal model shows local force induces an expanding stiffened region.

The stiffened region acts as an effective probe during local loading.

Abstract

Nonlinear stiffening is a ubiquitous property of major types of biopolymers that make up the extracellular matrices (ECM) including collagen, fibrin and basement membrane. Within the ECM, many types of cells such as fibroblasts and cancer cells are known to mechanically stretch their surroundings that locally stiffens the matrix. Although the bulk nonlinear elastic behaviors of these biopolymer networks are well studied, their local mechanical responses remain poorly characterized. Here, to understand how a living cell feels the nonlinear mechanical resistance from the ECM, we mimic the cell-applied local force using optical tweezers; we report that the local stiffening responses in highly nonlinear ECM are significantly weaker than responses found in bulk rheology, across two orders of magnitude of the locally applied force since the onset of stiffening. With a minimal model, we show that a local point force application can induce a stiffened region in the matrix, which expands with increasing magnitude of the point force. Furthermore, we show that this stiffened region behaves as an effective probe upon local loading. The local nonlinear elastic response can be attributed to the nonlinear growth of this effective probe that linearly deforms an increasing portion of the matrix.