title: The role of the dynamics of focal adhesion kinase in the mechanotaxis of endothelial cells.
abstract: The migration of vascular endothelial cells (ECs) is critical in vascular remodeling. We showed that fluid shear stress enhanced EC migration in flow direction and called this "mechanotaxis." To visualize the molecular dynamics of focal adhesion kinase (FAK) at focal adhesions (FAs), FAK tagged with green fluorescence protein (GFP) was expressed in ECs. Within 10 min of shear stress application, lamellipodial protrusion was induced at cell periphery in the flow direction, with the recruitment of FAK at FAs. ECs under flow migrated with polarized formation of new FAs in flow direction, and these newly formed FAs subsequently disassembled after the rear of the cell moved over them. The cells migrating under flow had a decreased number of FAs. In contrast to shear stress, serum did not significantly affect the speed of cell migration. Serum induced lamellipodia and FAK recruitment at FAs without directional preference. FAK(Y397) phosphorylation colocalized with GFP-FAK at FAs in both shear stress and serum experiments. The total level of FAK(Y397) phosphorylation after shear stress was lower than that after serum treatment, suggesting that the polarized change at cell periphery rather than the total level of FAK(Y397) phosphorylation is important for directional migration. Our results demonstrate the dynamics of FAK at FAs during the directional migration of EC in response to mechanical force, and suggest that mechanotaxis is an important mechanism controlling EC migration.
authors.affiliation: Department of Bioengineering and The Whitaker Institute of Biomedical Engineering, University of California at San Diego, La Jolla, CA 92093-0427, USA.
authors.forename: Song
authors.initials: S
authors.lastname: Li
authors.forename: Peter
authors.initials: P
authors.lastname: Butler
authors.forename: Yingxiao
authors.initials: Y
authors.lastname: Wang
authors.forename: Yingli
authors.initials: Y
authors.lastname: Hu
authors.forename: Dong Cho
authors.initials: DC
authors.lastname: Han
authors.forename: Shunichi
authors.initials: S
authors.lastname: Usami
authors.forename: Jun-Lin
authors.initials: JL
authors.lastname: Guan
authors.forename: Shu
authors.initials: S
authors.lastname: Chien
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D001704:Biopolymers / Q000378:metabolism; D002417:Cattle; D002465:Cell Movement / Q000187:drug effects; D016764:Cell Polarity; D003599:Cytoskeleton / Q000187:drug effects / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology*; D051416:Focal Adhesion Protein-Tyrosine Kinases; D022001:Focal Adhesions / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D018056:Hemorheology; D010766:Phosphorylation; D021381:Protein Transport / Q000187:drug effects; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011554:Pseudopodia / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D012709:Serum Albumin / Q000494:pharmacology
chemical_list: D000199:Actins; D001704:Biopolymers; D012709:Serum Albumin; D011505:Protein-Tyrosine Kinases; D051416:Focal Adhesion Protein-Tyrosine Kinases