Local 3D matrix microenvironment regulates cell migration through spatiotemporal dynamics of contractility-dependent adhesions

被引:362
作者
Doyle, Andrew D. [1 ]
Carvajal, Nicole [2 ]
Jin, Albert [2 ]
Matsumoto, Kazue [1 ]
Yamada, Kenneth M. [1 ]
机构
[1] Natl Inst Dent & Craniofacial Res, Lab Cell & Dev Biol, Cell Biol Sect, NIH, Bethesda, MD 20892 USA
[2] Natl Inst Biomed Imaging & Bioengn, Lab Cellular Imaging & Macromol Biophys, NIH, Bethesda, MD 20892 USA
关键词
3-DIMENSIONAL COLLAGEN MATRICES; ATOMIC-FORCE MICROSCOPY; FOCAL ADHESIONS; ACTIN CYTOSKELETON; NASCENT ADHESIONS; POISSONS RATIO; INTEGRIN; MECHANICS; LIMITS; MODEL;
D O I
10.1038/ncomms9720
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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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页数:15
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