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

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.