title: Local 3D matrix microenvironment regulates cell migration through spatiotemporal dynamics of contractility-dependent adhesions.
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.
authors.affiliation: Laboratory of Cell and Developmental Biology, Cell Biology Section, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Doyle
authors.affiliation: Laboratory of Cellular Imaging and Macromolecular Biophysics, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: Nicole
authors.initials: N
authors.lastname: Carvajal
authors.affiliation: Laboratory of Cellular Imaging and Macromolecular Biophysics, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: Albert
authors.identifier: http://orcid.org/0000-0003-3826-1081
authors.initials: A
authors.lastname: Jin
authors.affiliation: Laboratory of Cell and Developmental Biology, Cell Biology Section, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: Kazue
authors.initials: K
authors.lastname: Matsumoto
authors.affiliation: Laboratory of Cell and Developmental Biology, Cell Biology Section, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: Kenneth M
authors.initials: KM
authors.lastname: Yamada
mesh_terms: D000818:Animals; D002448:Cell Adhesion; D002465:Cell Movement; D060833:Cellular Microenvironment; D003094:Collagen / Q000378:metabolism; D003285:Contractile Proteins; D004548:Elasticity; D005109:Extracellular Matrix / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism*; D036681:Fluorescence Recovery After Photobleaching; D005455:Fluorescent Antibody Technique; D006801:Humans; D016023:Integrins / Q000378:metabolism*; D051379:Mice; D018625:Microscopy, Atomic Force; D024462:Myosin Type II / Q000378:metabolism*; D012867:Skin / Q000378:metabolism
chemical_list: D003285:Contractile Proteins; D016023:Integrins; D003094:Collagen; D024462:Myosin Type II