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Cells continuously probe their environment with membrane receptors, achievingsubsecond adaptation of their behaviour [1-3]. Recently, several receptors,including cadherins, were found to bind ligands with a lifetime of order of onesecond. Here we show at the single molecule level that homotypic C-cadherinassociation involves transient intermediates lasting less than a few tens ofmilliseconds. Further, these intermediates transitionned towards more stablestates with a kinetic rate displaying exponential decrease with piconewtonforces. These features enable cells to detect ligands or measure surroundingmechanical behaviour within a fraction of a second, much more rapidly than waspreviously thought.

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