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Beyond structure: mechanism and dynamics of intercellular adhesion

机译：超越结构：细胞间粘附的机制和动态

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摘要

This review summarizes findings from multiple complementary quantitative investigations of adhesion by classical cadherins. The systems investigated range from single molecules to cells, and the approaches used quantify the kinetics, energetics and mechanical strengths of cadherin bonds. The cumulative results demonstrate that cadherins adhere via a multistage binding mechanism that involves multiple extracellular domains. In kinetic measurements of cell adhesion, cell pairs first form a low-probability-binding state with fast kinetics. This is followed by a lag and a slow transition to a second, high-probability, binding state. This two-stage process is independent of the cytoplasmic domain. Studies with domain-deletion mutants demonstrate that the N-terminal domains are required for the first, fast, weak binding. However, the full-ectodomain and EC3 (extracellular repeat 3), in particular, are required to form the second, high-probability, binding state, which is characterized by slow dissociation kinetics and much stronger adhesive bonds. Together, these different studies reveal a more complex multistage binding mechanism than was predicted by structural models.
机译：本综述总结了经典钙丝粘附的多种互补定量研究的发现。该系统研究了从单分子到细胞的范围，并且使用该方法量化了钙粘蛋白键的动力学，能量和机械优势。累积结果表明，钙丝通过涉及多个细胞外结构域的多级结合机制粘附。在电池粘附的动力学测量中，细胞对首先形成具有快速动力学的低概率结合状态。这是滞后和慢速转换到第二，高概率，绑定状态。这种两级过程与细胞质结构域无关。具有域 - 缺失突变体的研究表明，第一，快速较弱的结合需要n末端域。然而，特别是全外域和EC3（细胞外重复3），特别是形成第二，高概率，结合状态，其特征在于缓慢解离动力学和更强的粘合剂键。这些不同的研究在一起揭示了比结构模型预测的更复杂的多级绑定机制。

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