Membrane fluctuations mediate lateral interaction between cadherin bonds

Fenz, Susanne F.; Schmidt, Daniel; Seifert, Udo; Sengupta, Kheya; Bihr, Timo; Smith, Ana-Sunčana; Merkel, Rudolf

doi:10.1038/nphys4138

Journal Article

FZJ-2017-04189

Membrane fluctuations mediate lateral interaction between cadherin bonds

Fenz, S. F. ; Bihr, T. ; Schmidt, D. ; Merkel, R.FZJ* ; Seifert, U. ; Sengupta, K. ; Smith, A.-S. (Corresponding author)

2017
Nature Publishing Group Basingstoke

Nature physics 13, 906–913 (2017) [10.1038/nphys4138]

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Please use a persistent id in citations: http://hdl.handle.net/2128/15921 doi:10.1038/nphys4138

Abstract: 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 trans-bonds. 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 affinity 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.

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