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.

中文翻译：

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膜波动介导钙粘蛋白键之间的横向相互作用

活组织的完整性通过位于相邻细胞相对膜上的钙黏着蛋白之间形成的反式键的粘附域来维持。这些域通过在同一细胞上的钙粘着蛋白之间的横向顺式相互作用来稳定。然而，顺式相互作用的起源仍然是困惑的，因为仅在反式键的情况下才检测到它们。通过结合实验，分析和计算方法，我们确定膜的弯曲波动是长距离顺式相互作用的源，也是反式调节剂-互动。具体地，纳米膜的弯曲和波动引入了协同效应，该协同效应调节了反式二聚作用的亲和力和结合/非结合速率，从而极大地影响了粘附域的成核和生长。重要的是，该法规依赖于物理原理，而不依赖于蛋白质间相互作用的细节。这些无所不在的波动因此可以充当所有类型细胞粘附中的通用控制机制，这暗示了对于最近发现的细胞膜活动性波动迄今未知的生理作用。