Active prestress leads to an apparent stiffening of cells through geometrical effects

TL;DR

This paper demonstrates that geometrical effects can cause an apparent stiffening in cells under active prestress, which mimics true stress-induced stiffening but is actually a geometric artifact, highlighting the need for improved experimental methods.

Contribution

The study provides a theoretical explanation for apparent cellular stiffening due to geometrical effects, distinct from actual changes in elastic modulus, challenging previous interpretations of experimental data.

Findings

Geometrical effects can produce apparent stress-stiffening in cells.

Apparent stiffening is disconnected from actual elastic modulus changes.

Experimental approaches must distinguish between geometric effects and true material nonlinearities.

Abstract

Tuning of active prestress e.g. through activity of molecular motors constitutes a powerful cellular tool to adjust cellular stiffness through nonlinear material properties. Understanding this tool is an important prerequisite for our comprehension of cellular force response, cell shape dynamics and tissue organisation. Experimental data obtained from cell-mechanical measurements often show a simple linear dependence between mechanical prestress and measured differential elastic moduli. While these experimental findings could point to stress-induced structural changes in the material, we propose here a surprisingly simple alternative explanation in a theoretical study. We show how geometrical effects can give rise to increased cellular force response of cells in the presence of active prestress. The associated effective stress-stiffening is disconnected from actual stress-induced changes of the elastic modulus and should therefore be regarded as an apparent stiffening of the material. We argue that new approaches in experimental design are necessary to separate this apparent stress-stiffening due to geometrical effects from actual nonlinearities of the elastic modulus in prestressed cellular material.