title: Flow-induced focal adhesion remodeling mediated by local cytoskeletal stresses and reorganization.
abstract: Cells respond to fluid shear stress through dynamic processes involving changes in actomyosin and other cytoskeletal stresses, remodeling of cell adhesions, and cytoskeleton reorganization. In this study we simultaneously measured focal adhesion dynamics and cytoskeletal stress and reorganization in MDCK cells under fluid shear stress. The measurements used co-expression of fluorescently labeled paxillin and force sensitive FRET probes of α-actinin. A shear stress of 0.74 dyn/cm(2) for 3 hours caused redistribution of cytoskeletal tension and significant focal adhesion remodeling. The fate of focal adhesions is determined by the stress state and stability of the linked actin stress fibers. In the interior of the cell, the mature focal adhesions disassembled within 35-40 min under flow and stress fibers disintegrated. Near the cell periphery, the focal adhesions anchoring the stress fibers perpendicular to the cell periphery disassembled, while focal adhesions associated with peripheral fibers sustained. The diminishing focal adhesions are coupled with local cytoskeletal stress release and actin stress fiber disassembly whereas sustaining peripheral focal adhesions are coupled with an increase in stress and enhancement of actin bundles. The results show that flow induced formation of peripheral actin bundles provides a favorable environment for focal adhesion remodeling along the cell periphery. Under such condition, new FAs were observed along the cell edge under flow. Our results suggest that the remodeling of FAs in epithelial cells under flow is orchestrated by actin cytoskeletal stress redistribution and structural reorganization.
authors.affiliation: b Department of Mechanical and Aerospace Engineering ; SUNY-Buffalo ; Buffalo , NY USA.
authors.forename: Deepika
authors.initials: D
authors.lastname: Verma
authors.affiliation: a Department of Physiology and Biophysics ; SUNY-Buffalo , Buffalo , NY USA.
authors.forename: Fanjie
authors.initials: F
authors.lastname: Meng
authors.affiliation: a Department of Physiology and Biophysics ; SUNY-Buffalo , Buffalo , NY USA.
authors.forename: Frederick
authors.initials: F
authors.lastname: Sachs
authors.affiliation: a Department of Physiology and Biophysics ; SUNY-Buffalo , Buffalo , NY USA.|b Department of Mechanical and Aerospace Engineering ; SUNY-Buffalo ; Buffalo , NY USA.
authors.forename: Susan Z
authors.initials: SZ
authors.lastname: Hua
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism / Q000648:ultrastructure; D000185:Actinin / Q000378:metabolism; D000199:Actins / Q000378:metabolism; D000818:Animals; D002448:Cell Adhesion / Q000235:genetics*; D002465:Cell Movement; D004285:Dogs; D004847:Epithelial Cells / Q000378:metabolism / Q000648:ultrastructure*; D022001:Focal Adhesions / Q000378:metabolism*; D006801:Humans; D061985:Madin Darby Canine Kidney Cells; D022502:Stress Fibers / Q000378:metabolism / Q000648:ultrastructure; D013314:Stress, Mechanical
chemical_list: D000199:Actins; D000185:Actinin
keywords: FRET; MDCK cells; cytoskeletal force; focal adhesions; mechanotransduction