细胞外基质
整合素
收缩性
粘附
细胞生物学
细胞粘附
焦点粘着
纤维连接蛋白
化学
机械转化
细胞迁移
生物物理学
细胞
生物
生物化学
信号转导
有机化学
内分泌学
作者
Andrew D. Doyle,Nicole Carvajal,Albert J. Jin,Kazue Matsumoto,Kenneth M. Yamada
摘要
Abstract The physical properties of two-dimensional (2D) extracellular matrices (ECMs) modulate cell adhesion dynamics and motility, but little is known about the roles of local microenvironmental differences in three-dimensional (3D) ECMs. Here we generate 3D collagen gels of varying matrix microarchitectures to characterize their regulation of 3D adhesion dynamics and cell migration. ECMs containing bundled fibrils demonstrate enhanced local adhesion-scale stiffness and increased adhesion stability through balanced ECM/adhesion coupling, whereas highly pliable reticular matrices promote adhesion retraction. 3D adhesion dynamics are locally regulated by ECM rigidity together with integrin/ECM association and myosin II contractility. Unlike 2D migration, abrogating contractility stalls 3D migration regardless of ECM pore size. We find force is not required for clustering of activated integrins on 3D native collagen fibrils. We propose that efficient 3D migration requires local balancing of contractility with ECM stiffness to stabilize adhesions, which facilitates the detachment of activated integrins from ECM fibrils.
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