Dissecting subsecond cadherin bound states reveals an efficient way for cells to achieve ultrafast probing of their environment.

Anne Pierres (1) , Anil Prakasam (2) , Dominique Touchard (1) , Anne-Marie Benoliel (1) , Pierre Bongrand (1) , Deborah Leckband (2)

1 LAI - Adhésion et Inflammation
2 Department of Chemical and Biochemical Engineering

Cells continuously probe their environment with membrane receptors, achieving subsecond adaptation of their behaviour [Diez, G., Gerisch, G., Anderson, K., M?r-Taubenberger, A. and Bretschneider, T. (2006) Subsecond reorganization of the actin network in cell motility and chemotaxis. Proc. Natl. Acad. Sci. USA 102, 7601-7606, Shamri, R., Grabovsky, V., Gauguet, J.M., Feigelson, S., Manevich, E., Kolanus, W., Robinson, M.K., Staunton, D.E., von Andrian, U.H. and Alon, R. (2005) Lymphocyte arrest requires instantaneous induction of an extended LFA-1 conformation mediated by endothelium-bound chemokines. Nat. Immunol. 6, 497-606, Jiang, G., Huang, A.H., Cai, Y., Tanase, M. and Sheetz, M.P. (2006) Rigidity sensing at the leading edge through alpha(V)beta(3) integrins and RPTPalpha. Biophys. J. 90, 1804-2006]. 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.

Mots clés: flow chamber; binding kinetics; molecular forces; cadherins

Domaines: Biophysique; Interactions cellulaires [q-bio.CB]; Biophysique [physics.bio-ph]

Anne Pierres, Anil Prakasam, Dominique Touchard, Anne-Marie Benoliel, Pierre Bongrand, et al.. Dissecting subsecond cadherin bound states reveals an efficient way for cells to achieve ultrafast probing of their environment.. FEBS Letters, 2007, 581 (9), pp.1841-6. ⟨10.1016/j.febslet.2007.03.077⟩. ⟨hal-00174304⟩