整合素介导的粘着斑是在细胞外基质（ECM）和肌动蛋白细胞骨架之间传递力的主要结构。尽管在支持高机械张力的刚性和平坦基材上粘着斑丰富，但在柔软的三维 (3D) 环境中粘着斑却很少。在这里，我们报告曲率依赖性整合素介导的粘连，称为弯曲粘连。它们的形成受到 ECM 蛋白纤维的形貌所施加的膜曲率的调节。弯曲粘连由整合素 ɑvβ5 介导，在分子上不同于粘着斑和网格蛋白晶格。该分子机制涉及整合素 β5 和曲率感应蛋白 FCHo2 之间以前未知的相互作用。我们发现弯曲粘连在生理条件下很普遍，并且弯曲粘连的破坏会抑制 3D 纤维基质中某些癌细胞系的迁移。这些发现提供了细胞锚定到天然蛋白质纤维的机制，并表明弯曲的粘连可以作为潜在的治疗靶点。© 2023。作者。

Integrin-mediated focal adhesions are the primary architectures that transmit forces between the extracellular matrix (ECM) and the actin cytoskeleton. Although focal adhesions are abundant on rigid and flat substrates that support high mechanical tensions, they are sparse in soft three-dimensional (3D) environments. Here we report curvature-dependent integrin-mediated adhesions called curved adhesions. Their formation is regulated by the membrane curvatures imposed by the topography of ECM protein fibres. Curved adhesions are mediated by integrin ɑvβ5 and are molecularly distinct from focal adhesions and clathrin lattices. The molecular mechanism involves a previously unknown interaction between integrin β5 and a curvature-sensing protein, FCHo2. We find that curved adhesions are prevalent in physiological conditions, and disruption of curved adhesions inhibits the migration of some cancer cell lines in 3D fibre matrices. These findings provide a mechanism for cell anchorage to natural protein fibres and suggest that curved adhesions may serve as a potential therapeutic target.© 2023. The Author(s).