Journal
NATURE PHYSICS
Volume 13, Issue 9, Pages 906-913Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/NPHYS4138
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Funding
- ERC-StG of the European Research Council [307104FP]
- Research Training Group 1962 at the Friedrich-Alexander-Universitat Erlangen-Nurnberg
- A*MIDEX [ANR-11-IDEX-0001-02]
- Croatian Science Foundation [IP-11-2013-8238 CompSoLS-MolFlex]
- BigThera project at FAU
- [ERC StG 2013-337283]
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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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