Physical limits on cellular directional mechanosensing

TL;DR

This paper investigates the physical and biological limits of how eukaryotic cells sense the direction of mechanical stimuli through mechanosensitive channels, revealing factors that enhance or constrain this sensing ability.

Contribution

It introduces a biophysical model of mechanosensitive channel activation and analyzes the physical constraints on cellular directional mechanosensing under shear flow.

Findings

Sensing accuracy improves with cell size and signal exposure.

Near-critical membrane prestress enhances sensing precision.

A nonlinear threshold limits sensing at low signal-to-noise ratios.

Abstract

Many eukaryotic cells are able to perform directional mechanosensing by directly measuring minute spatial differences in the mechanical stress on their membranes. Here, we explore the limits of a single mechanosensitive channel activation using a two-state double-well model for the gating mechanism. We then focus on the physical limits of directional mechanosensing by a single cell having multiple mechanosensors and subjected to a shear flow inducing a nonuniform membrane tension. Our results demonstrate that the accuracy in sensing the mechanostimulus direction not only increases with cell size and exposure to a signal, but also grows for cells with a near-critical membrane prestress. Finally, the existence of a nonlinear threshold effect, fundamentally limiting the cell's ability to effectively perform directional mechanosensing at a low signal-to-noise ratio, is uncovered.