Dissecting Subsecond Cadherin Bound States Reveals an Efficient Way for Cells to Achieve Ultrafast Probing of their Environment

TL;DR

This study reveals that C-cadherin receptors can rapidly switch between transient and stable states within milliseconds, enabling cells to quickly sense their environment and respond in less than a second.

Contribution

The paper uncovers the ultrafast dynamics of cadherin binding states at the single-molecule level, demonstrating a new mechanism for rapid environmental probing by cells.

Findings

Transient intermediates last less than a few tens of milliseconds.

Stable states form with a kinetic rate decreasing exponentially under force.

Cells can detect environmental cues within a fraction of a second.

Abstract

Cells continuously probe their environment with membrane receptors, achieving subsecond adaptation of their behaviour [1-3]. Recently, several receptors, including cadherins, were found to bind ligands with a lifetime of order of one second. Here we show at the single molecule level that homotypic C-cadherin association involves transient intermediates lasting less than a few tens of milliseconds. Further, these intermediates transitionned towards more stable states with a kinetic rate displaying exponential decrease with piconewton forces. These features enable cells to detect ligands or measure surrounding mechanical behaviour within a fraction of a second, much more rapidly than was previously thought.