Membrane fluctuations mediate lateral interaction between cadherin bonds

Fenz, Susanne F.; Bihr, Timo; Schmidt, Daniel; Merkel, Rudolf; Seifert, Udo; Sengupta, Kheya; Smith, Ana-Sunčana (2017) Membrane fluctuations mediate lateral interaction between cadherin bonds. Nature Physics, 13 (9). pp. 906-913. ISSN 1745-2473

| Request a personal copy from author

Official URL: https://www.nature.com/articles/nphys4138?WT.feed_...

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 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.

Item Type:

Article

Additional Information:

A.-S.S. and T.B. were funded from the grant ERC StG 2013-337283 and K.S. from ERC-StG 307104FP of the European Research Council. A.-S.S. and D.S. were supported by the Research Training Group 1962 at the Friedrich-Alexander-Universitat Erlangen-Nurnberg. This work has partly been supported by A*MIDEX (no. ANR-11-IDEX-0001-02), the Croatian Science Foundation (IP-11-2013-8238 CompSoLS-MolFlex) and the BigThera project at FAU.

Uncontrolled Keywords:

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

Subjects:

NATURAL SCIENCES > Physics

Divisions:

Division of Physical Chemistry

Projects: