engleski

Membrane fluctuations mediate lateral interaction between cadherin bonds

The integrity of living tissues is maintained by adhesion domains of trans-bonds formed between cadherin proteins residing on opposing membranes of neighbouring cells. These domains are stabilized by lateral cis- interactions between the cadherins on the same cell. However, the origin of cis- interactions remains perplexing since they are detected only in the context of transbonds. By combining experimental, analytical and computational approaches, we identify bending fluctuations of membranes as a source of long-range cis- interactions, and a regulator of trans- interactions. Specifically, nanometric membrane bending and fluctuations introduce cooperative effects that modulate the affnity and binding/unbinding rates for trans-dimerization, dramatically affecting the nucleation and growth of adhesion domains. Importantly, this regulation relies on physical principles and not on details of protein–protein interactions. These omnipresent fluctuations can thus act as a generic control mechanism in all types of cell adhesion, suggesting a hitherto unknown physiological role for recently identified active fluctuations of cellular membranes.

interference contrast microscopy ; cell-adhesion ; adherens junctions ; giant vesicles ; i cadherins ; binding ; dynamics ; domains ; actin ; specificity

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