Mechanotransduction in endothelial cell migration

The migration of endothelial cells (ECs) plays an important role in vascular remodeling and regeneration. EC migration can be regulated by different mechanisms such as chemotaxis, haptotaxis, and mechanotaxis. This review will focus on fluid shear stress‐induced mechanotransduction during EC migration. EC migration and mechanotransduction can be modulated by cytoskeleton, cell surface receptors such as integrins and proteoglycans, the chemical and physical properties of extracellular matrix (ECM) and cell–cell adhesions. The shear stress applied on the luminal surface of ECs can be sensed by cell membrane and associated receptor and transmitted throughout the cell to cell–ECM adhesions and cell–cell adhesions. As a result, shear stress induces directional migration of ECs by promoting lamellipodial protrusion and the formation of focal adhesions (FAs) at the front in the flow direction and the disassembly of FAs at the rear. Persistent EC migration in the flow direction can be driven by polarized activation of signaling molecules and the positive feedback loops constituted by Rho GTPases, cytoskeleton, and FAs at the leading edge. Furthermore, shear stress‐induced EC migration can overcome the haptotaxis of ECs. Given the hemodynamic environment of the vascular system, mechanotransduction during EC migration has a significant impact on vascular development, angiogenesis, and vascular wound healing. J. Cell. Biochem. © 2005 Wiley‐Liss, Inc.

[1]  K. Fujiwara,et al.  The biased lamellipodium development and microtubule organizing center position in vascular endothelial cells migrating under the influence of fluid flow * , 1993, Biology of the cell.

[2]  G. Schultz,et al.  The G-protein G13 but Not G12 Mediates Signaling from Lysophosphatidic Acid Receptor via Epidermal Growth Factor Receptor to Rho* , 1998, The Journal of Biological Chemistry.

[3]  J. Tarbell,et al.  Shear stress regulates occludin content and phosphorylation. , 2001, American journal of physiology. Heart and circulatory physiology.

[4]  I. Gelfand,et al.  Effect of microtubule-destroying drugs on the spreading and shape of cultured epithelial cells. , 1985, Journal of cell science.

[5]  L. McIntire,et al.  Mechanical effects on endothelial cell morphology: In vitro assessment , 1986, In Vitro Cellular & Developmental Biology.

[6]  A. Flozak,et al.  Wound Closure in Sheared Endothelial Cells is Enhanced by Modulation of Vascular Endothelial-Cadherin Expression and Localization , 2002, Experimental biology and medicine.

[7]  M. Monden,et al.  Gradients in cytoplasmic calcium concentration ([Ca2+]i) in migrating human umbilical vein endothelial cells (HUVECs) stimulated by shear-stress. , 1999, Life sciences.

[8]  G. Nemerow,et al.  Differential regulation of cell motility and invasion by FAK , 2003, The Journal of cell biology.

[9]  A. Woods,et al.  Adhesion and cytoskeletal organisation of fibroblasts in response to fibronectin fragments. , 1986, The EMBO journal.

[10]  B. Chen,et al.  Differential regulation of Rho GTPases by beta1 and beta3 integrins: the role of an extracellular domain of integrin in intracellular signaling. , 2002, Journal of cell science.

[11]  A. Arcaro The Small GTP-binding Protein Rac Promotes the Dissociation of Gelsolin from Actin Filaments in Neutrophils* , 1998, The Journal of Biological Chemistry.

[12]  Y. Wang,et al.  High resolution detection of mechanical forces exerted by locomoting fibroblasts on the substrate. , 1999, Molecular biology of the cell.

[13]  J. Mao,et al.  Guanine nucleotide exchange factor GEF115 specifically mediates activation of Rho and serum response factor by the G protein alpha subunit Galpha13. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[14]  M. Crow,et al.  Shear stress-mediated cytoskeletal remodeling and cortactin translocation in pulmonary endothelial cells. , 2002, American journal of respiratory cell and molecular biology.

[15]  T. Enomoto,et al.  Microtubule disruption induces the formation of actin stress fibers and focal adhesions in cultured cells: possible involvement of the rho signal cascade. , 1996, Cell structure and function.

[16]  S. Shapiro,et al.  Contribution of Monocytes/Macrophages to Compensatory Neovascularization: The Drilling of Metalloelastase-Positive Tunnels in Ischemic Myocardium , 2000, Circulation research.

[17]  A. Bershadsky,et al.  Pseudopodial activity at the active edge of migrating fibroblast is decreased after drug-induced microtubule depolymerization. , 1991, Cell motility and the cytoskeleton.

[18]  T. Hunter,et al.  Fluid Shear Stress Activation of Focal Adhesion Kinase , 1997, The Journal of Biological Chemistry.

[19]  A. Reynolds,et al.  The p120 catenin family: complex roles in adhesion, signaling and cancer. , 2000, Journal of cell science.

[20]  P. Oh,et al.  In Situ Flow Activates Endothelial Nitric Oxide Synthase in Luminal Caveolae of Endothelium with Rapid Caveolin Dissociation and Calmodulin Association* , 1998, The Journal of Biological Chemistry.

[21]  M. Schwartz,et al.  Focal adhesion kinase suppresses Rho activity to promote focal adhesion turnover. , 2000, Journal of cell science.

[22]  D. Schlaepfer,et al.  Signaling through focal adhesion kinase. , 1999, Progress in biophysics and molecular biology.

[23]  E. Dejana,et al.  Regulation of cadherin function by Rho and Rac: modulation by junction maturation and cellular context. , 1999, Molecular biology of the cell.

[24]  S. Chien,et al.  Integrin-mediated mechanotransduction requires its dynamic interaction with specific extracellular matrix (ECM) ligands. , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[25]  A. Gohla,et al.  Interaction of G protein Gβγ dimers with small GTP‐binding proteins of the Rho family , 1996 .

[26]  Miguel A del Pozo,et al.  Localized Cdc42 Activation, Detected Using a Novel Assay, Mediates Microtubule Organizing Center Positioning in Endothelial Cells in Response to Fluid Shear Stress* , 2003, Journal of Biological Chemistry.

[27]  E. Nishida,et al.  Cofilin phosphorylation by LIM-kinase 1 and its role in Rac-mediated actin reorganization , 1998, Nature.

[28]  K. Burridge,et al.  Rho-mediated Contractility Exposes a Cryptic Site in Fibronectin and Induces Fibronectin Matrix Assembly , 1998, The Journal of cell biology.

[29]  Shu Chien,et al.  Activation of integrins in endothelial cells by fluid shear stress mediates Rho‐dependent cytoskeletal alignment , 2001, The EMBO journal.

[30]  M. Schwartz,et al.  Suppression of Integrin Activation: A Novel Function of a Ras/Raf-Initiated MAP Kinase Pathway , 1997, Cell.

[31]  Shu Chien,et al.  Role of integrins in endothelial mechanosensing of shear stress. , 2002, Circulation research.

[32]  S. Carter,et al.  Haptotaxis and the Mechanism of Cell Motility , 1967, Nature.

[33]  J. Guan,et al.  Integrin-mediated signal transduction pathways. , 1999, Histology and histopathology.

[34]  L R Sauvage,et al.  Effect of differential shear stress on platelet aggregation, surface thrombosis, and endothelialization of bilateral carotid-femoral grafts in the dog. , 1995, Journal of vascular surgery.

[35]  Y. Takada,et al.  Distinct functions of integrin alpha and beta subunit cytoplasmic domains in cell spreading and formation of focal adhesions , 1993, The Journal of cell biology.

[36]  D. C. Edwards,et al.  Activation of LIM-kinase by Pak1 couples Rac/Cdc42 GTPase signalling to actin cytoskeletal dynamics , 1999, Nature Cell Biology.

[37]  S. Santoro,et al.  Alteration of collagen-dependent adhesion, motility, and morphogenesis by the expression of antisense alpha 2 integrin mRNA in mammary cells. , 1995, Journal of cell science.

[38]  B L Langille,et al.  Transient and steady-state effects of shear stress on endothelial cell adherens junctions. , 1999, Circulation research.

[39]  Melody A. Swartz,et al.  Interstitial Flow as a Guide for Lymphangiogenesis , 2003, Circulation research.

[40]  H. Schnittler,et al.  Role of cadherins and plakoglobin in interendothelial adhesion under resting conditions and shear stress. , 1997, The American journal of physiology.

[41]  A. Woods,et al.  Syndecan-4 and integrins: combinatorial signaling in cell adhesion. , 1999, Journal of cell science.

[42]  Girard Pr,et al.  Endothelial cell signaling and cytoskeletal changes in response to shear stress. , 1993 .

[43]  Gary M. Bokoch,et al.  Regulation of leading edge microtubule and actin dynamics downstream of Rac1 , 2003, The Journal of cell biology.

[44]  S Esser,et al.  Cell confluence regulates tyrosine phosphorylation of adherens junction components in endothelial cells. , 1997, Journal of cell science.

[45]  H. Schnittler Structural and functional aspects of intercellular junctions in vascular endothelium , 1998, Basic Research in Cardiology.

[46]  A. Woods,et al.  Control of morphology, cytoskeleton and migration by syndecan-4. , 1999, Journal of cell science.

[47]  V. Quaranta,et al.  Integrin cytoplasmic domains mediate inside-out signal transduction , 1994, The Journal of cell biology.

[48]  H. Schnaper,et al.  Shear stress enhances human endothelial cell wound closure in vitro. , 2000, American journal of physiology. Heart and circulatory physiology.

[49]  J A Frangos,et al.  Fluid shear stress increases membrane fluidity in endothelial cells: a study with DCVJ fluorescence. , 2000, American journal of physiology. Heart and circulatory physiology.

[50]  Anne J. Ridley,et al.  The small GTP-binding protein rac regulates growth factor-induced membrane ruffling , 1992, Cell.

[51]  K. Yamada,et al.  "Inside-out" signal transduction inhibited by isolated integrin cytoplasmic domains. , 1994, The Journal of biological chemistry.

[52]  Milan Mrksich,et al.  Geometric control of switching between growth, apoptosis, and differentiation during angiogenesis using micropatterned substrates , 1999, In Vitro Cellular & Developmental Biology - Animal.

[53]  George E. Davis,et al.  Capillary morphogenesis during human endothelial cell invasion of three-dimensional collagen matrices , 2000, In Vitro Cellular & Developmental Biology - Animal.

[54]  D. Ingber Tensegrity I. Cell structure and hierarchical systems biology , 2003, Journal of Cell Science.

[55]  T. Chung,et al.  Growth of human endothelial cells on different concentrations of Gly-Arg-Gly-Asp grafted chitosan surface. , 2003, Artificial organs.

[56]  P. Keely,et al.  Integrins and GTPases in tumour cell growth, motility and invasion. , 1998, Trends in cell biology.

[57]  C. ffrench-Constant,et al.  Neural precursor cell chain migration and division are regulated through different beta1 integrins. , 1998, Development.

[58]  S. Bhatia,et al.  Effects of morphological patterning on endothelial cell migration. , 2001, Biorheology.

[59]  C. García-echeverría,et al.  Synthesis, surface, and cell-adhesion properties of polyurethanes containing covalently grafted RGD-peptides. , 1994, Journal of biomedical materials research.

[60]  Y. Takada,et al.  Distinct Functions of Integrin ct and/3 Subunit Cytoplasmic Domains in Cell Spreading and Formation of Focal Adhesions , 1993 .

[61]  M. Sheetz,et al.  Cell migration: regulation of force on extracellular-matrix-integrin complexes. , 1998, Trends in cell biology.

[62]  M. Schwartz,et al.  Rac recruits high-affinity integrin αvβ3 to lamellipodia in endothelial cell migration , 2001, Nature Cell Biology.

[63]  J. Cooper,et al.  Control of actin assembly and disassembly at filament ends. , 2000, Current opinion in cell biology.

[64]  P. Dieterich,et al.  Role of actin filaments in endothelial cell-cell adhesion and membrane stability under fluid shear stress , 2001, Pflügers Archiv.

[65]  D R Critchley,et al.  Focal adhesions - the cytoskeletal connection. , 2000, Current opinion in cell biology.

[66]  R. Kramer,et al.  β1 And β3 integrins have different roles in the adhesion and migration of vascular smooth muscle cells on extracellular matrix , 1992 .

[67]  T. Pollard,et al.  Scar, a WASp-related protein, activates nucleation of actin filaments by the Arp2/3 complex. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[68]  B. Chen,et al.  Signal Transduction in Matrix Contraction and the Migration of Vascular Smooth Muscle Cells in Three-Dimensional Matrix , 2003, Journal of Vascular Research.

[69]  A. Sonnenberg,et al.  Laminin receptor on platelets is the integrin VLA-6 , 1988, Nature.

[70]  W. Kiosses,et al.  Regulation of the small GTP‐binding protein Rho by cell adhesion and the cytoskeleton , 1999, The EMBO journal.

[71]  Takayuki Kato,et al.  Cooperation between mDia1 and ROCK in Rho-induced actin reorganization , 1999, Nature Cell Biology.

[72]  Brian P. Helmke,et al.  The Cytoskeleton Under External Fluid Mechanical Forces: Hemodynamic Forces Acting on the Endothelium , 2002, Annals of Biomedical Engineering.

[73]  J. Frangos,et al.  PECAM-1 Interacts With Nitric Oxide Synthase in Human Endothelial Cells: Implication for Flow-Induced Nitric Oxide Synthase Activation , 2004, Arteriosclerosis, thrombosis, and vascular biology.

[74]  A. Gotlieb,et al.  Microtubule-organizing centers and cell migration: effect of inhibition of migration and microtubule disruption in endothelial cells , 1983, The Journal of cell biology.

[75]  Douglas B. Cowan,et al.  Regulation of vascular connexin43 gene expression by mechanical loads. , 1998, Circulation research.

[76]  L. Romer,et al.  Inhibition of focal adhesion kinase (FAK) signaling in focal adhesions decreases cell motility and proliferation. , 1996, Molecular biology of the cell.

[77]  C. Saxe,et al.  SCAR, a WASP-related Protein, Isolated as a Suppressor of Receptor Defects in Late Dictyostelium Development , 1998, The Journal of cell biology.

[78]  A. Mikhailov,et al.  Relationship between microtubule dynamics and lamellipodium formation revealed by direct imaging of microtubules in cells treated with nocodazole or taxol. , 1998, Cell motility and the cytoskeleton.

[79]  P. Hawkins,et al.  Activation of the small GTP-binding proteins rho and rac by growth factor receptors. , 1995, Journal of cell science.

[80]  Christopher S. Chen,et al.  Cells lying on a bed of microneedles: An approach to isolate mechanical force , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[81]  P. Davies,et al.  Quantitative studies of endothelial cell adhesion. Directional remodeling of focal adhesion sites in response to flow forces. , 1994, The Journal of clinical investigation.

[82]  N. Sugimoto,et al.  Inhibitory and Stimulatory Regulation of Rac and Cell Motility by the G12/13-Rho and Gi Pathways Integrated Downstream of a Single G Protein-Coupled Sphingosine-1-Phosphate Receptor Isoform , 2003, Molecular and Cellular Biology.

[83]  Brånemark Pi Capillary form and function. The microcirculation of granulation tissue. , 1965, Bibliotheca anatomica.

[84]  N. Chou,et al.  Growth of endothelial cells on different concentrations of Gly-Arg-Gly-Asp photochemically grafted in polyethylene glycol modified polyurethane. , 2001, Artificial organs.

[85]  Stephen C. Cowin,et al.  Mechanotransduction and flow across the endothelial glycocalyx , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[86]  A. Malik,et al.  VE-cadherin-induced Cdc42 Signaling Regulates Formation of Membrane Protrusions in Endothelial Cells* , 2003, The Journal of Biological Chemistry.

[87]  J. Hartwig,et al.  WIP, a protein associated with wiskott-aldrich syndrome protein, induces actin polymerization and redistribution in lymphoid cells. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[88]  A. Woods,et al.  A synthetic peptide from the COOH-terminal heparin-binding domain of fibronectin promotes focal adhesion formation. , 1993, Molecular biology of the cell.

[89]  J. Gutkind,et al.  The small GTP-binding protein Rho links G protein-coupled receptors and Galpha12 to the serum response element and to cellular transformation. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[90]  K. Burridge,et al.  Microtubule depolymerization induces stress fibers, focal adhesions, and DNA synthesis via the GTP-binding protein Rho. , 1998, Cell adhesion and communication.

[91]  E. Chaikof,et al.  α4β1 and α5β1 Control Cell Migration on Fibronectin by Differentially Regulating Cell Speed and Motile Cell Phenotype , 1998, Annals of Biomedical Engineering.

[92]  P. Caroni,et al.  Regulation of actin dynamics through phosphorylation of cofilin by LIM-kinase , 1998, Nature.

[93]  C. Nobes,et al.  Rho, Rac, and Cdc42 GTPases regulate the assembly of multimolecular focal complexes associated with actin stress fibers, lamellipodia, and filopodia , 1995, Cell.

[94]  Shiro Suetsugu,et al.  WAVE, a novel WASP‐family protein involved in actin reorganization induced by Rac , 1998, The EMBO journal.

[95]  M. Detmar,et al.  Angiogenesis promoted by vascular endothelial growth factor: regulation through alpha1beta1 and alpha2beta1 integrins. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[96]  R. Beyth,et al.  Complementary adhesive responses of human skin fibroblasts to the cell-binding domain of fibronectin and the heparan sulfate-binding protein, platelet factor-4. , 1984, Experimental cell research.

[97]  M. Woolkalís,et al.  Regulation of VE-cadherin linkage to the cytoskeleton in endothelial cells exposed to fluid shear stress. , 2002, Experimental cell research.

[98]  Richard G. W. Anderson,et al.  Sites of Ca(2+) wave initiation move with caveolae to the trailing edge of migrating cells. , 2002, Journal of cell science.

[99]  Frans,et al.  Loss of epithelial differentiation and gain of invasiveness correlates with tyrosine phosphorylation of the E-cadherin/beta-catenin complex in cells transformed with a temperature-sensitive v-SRC gene , 1993, The Journal of cell biology.

[100]  C. Turner,et al.  Tyrosine phosphorylation of paxillin and pp125FAK accompanies cell adhesion to extracellular matrix: a role in cytoskeletal assembly , 1992, The Journal of cell biology.

[101]  R M Nerem,et al.  The elongation and orientation of cultured endothelial cells in response to shear stress. , 1985, Journal of biomechanical engineering.

[102]  T. Hunter,et al.  Integrin-mediated signal transduction linked to Ras pathway by GRB2 binding to focal adhesion kinase , 1994, Nature.

[103]  M. Kinch,et al.  Integrin-mediated cell adhesion activates mitogen-activated protein kinases. , 1994, The Journal of biological chemistry.

[104]  A. Ridley Rho GTPases and cell migration. , 2001, Journal of cell science.

[105]  A. Hall,et al.  The assembly of integrin adhesion complexes requires both extracellular matrix and intracellular rho/rac GTPases , 1995, The Journal of cell biology.

[106]  A. Zeiher,et al.  Shear Stress–Induced Endothelial Cell Migration Involves Integrin Signaling Via the Fibronectin Receptor Subunits α5 and β1 , 2002 .

[107]  Micah Dembo,et al.  Rho mediates the shear-enhancement of endothelial cell migration and traction force generation. , 2004, Biophysical journal.

[108]  D A Lauffenburger,et al.  Maximal migration of human smooth muscle cells on fibronectin and type IV collagen occurs at an intermediate attachment strength , 1993, The Journal of cell biology.

[109]  S. Tumova,et al.  Syndecan-4 binding to the high affinity heparin-binding domain of fibronectin drives focal adhesion formation in fibroblasts. , 2000, Archives of biochemistry and biophysics.

[110]  A M Malek,et al.  Mechanism of endothelial cell shape change and cytoskeletal remodeling in response to fluid shear stress. , 1996, Journal of cell science.

[111]  E. Salmon,et al.  Microtubule growth activates Rac1 to promote lamellipodial protrusion in fibroblasts , 1999, Nature Cell Biology.

[112]  M. Schwartz,et al.  Integrins: emerging paradigms of signal transduction. , 1995, Annual review of cell and developmental biology.

[113]  R. Franke,et al.  Induction of human vascular endothelial stress fibres by fluid shear stress , 1984, Nature.

[114]  Shu Chien,et al.  Mechanotransduction in Response to Shear Stress , 1999, The Journal of Biological Chemistry.

[115]  M. Schwartz,et al.  Signaling networks linking integrins and rho family GTPases. , 2000, Trends in biochemical sciences.

[116]  T. Takenawa,et al.  The essential role of profilin in the assembly of actin for microspike formation , 1998, The EMBO journal.

[117]  S. Hanks,et al.  Identification of p130Cas as a Mediator of Focal Adhesion Kinase–promoted Cell Migration , 1998, The Journal of cell biology.

[118]  R. Kramer,et al.  Beta 1 and beta 3 integrins have different roles in the adhesion and migration of vascular smooth muscle cells on extracellular matrix. , 1992, Experimental cell research.

[119]  E. Tsilibary,et al.  Differential effects of laminin, intact type IV collagen, and specific domains of type IV collagen on endothelial cell adhesion and migration , 1988, The Journal of cell biology.

[120]  J. Squire,et al.  Quasi-periodic substructure in the microvessel endothelial glycocalyx: a possible explanation for molecular filtering? , 2001, Journal of structural biology.

[121]  H C van der Mei,et al.  Fluid shear induced endothelial cell detachment from glass--influence of adhesion time and shear stress. , 1994, Medical Engineering and Physics.

[122]  K. Fujiwara,et al.  Evidence for a role of platelet endothelial cell adhesion molecule-1 in endothelial cell mechanosignal transduction , 2002, The Journal of cell biology.

[123]  P. Branemark Capillary form and function. The microcirculation of granulation tissue. , 1965, Bibliotheca anatomica.

[124]  V. Gahtan,et al.  Role of p38 MAP kinase in endothelial cell alignment induced by fluid shear stress. , 2001, American journal of physiology. Heart and circulatory physiology.

[125]  Young-Mi Go,et al.  Plasma Membrane Cholesterol Is a Key Molecule in Shear Stress-dependent Activation of Extracellular Signal-regulated Kinase* , 1998, The Journal of Biological Chemistry.

[126]  G. Forgacs On the possible role of cytoskeletal filamentous networks in intracellular signaling: an approach based on percolation. , 1995, Journal of cell science.

[127]  C. S. Chen,et al.  Geometric control of cell life and death. , 1997, Science.

[128]  H. Mohri Interaction of Fibronectin With Integrin Receptors Evidence by Use of Synthetic Peptides , 1997, Peptides.

[129]  A. Bershadsky,et al.  Microtubule involvement in regulating cell contractility and adhesion-dependent signalling: a possible mechanism for polarization of cell motility. , 1999, Biochemical Society symposium.

[130]  E Ruoslahti,et al.  New perspectives in cell adhesion: RGD and integrins. , 1987, Science.

[131]  S. Weinbaum,et al.  Shear stress induces a time- and position-dependent increase in endothelial cell membrane fluidity. , 2001, American journal of physiology. Cell physiology.

[132]  J. Thiery,et al.  Neural crest cell locomotion induced by antibodies to beta 1 integrins. A tool for studying the roles of substratum molecular avidity and density in migration. , 1991, Journal of cell science.

[133]  A. Hall,et al.  Rac/Cdc42 and p65PAK Regulate the Microtubule-destabilizing Protein Stathmin through Phosphorylation at Serine 16* , 2001, The Journal of Biological Chemistry.

[134]  M. Monden,et al.  Shear-stress causes polarized change in cytoplasmic calcium concentration in human umbilical vein endothelial cells (HUVECs). , 1997, Cell calcium.

[135]  L. Addadi,et al.  Force and focal adhesion assembly: a close relationship studied using elastic micropatterned substrates , 2001, Nature Cell Biology.

[136]  Shu Chien,et al.  Shear stress-induced c-fos activation is mediated by Rho in a calcium-dependent manner. , 2003, Biochemical and biophysical research communications.

[137]  B. Chen,et al.  Distinct roles for the small GTPases Cdc42 and Rho in endothelial responses to shear stress. , 1999, The Journal of clinical investigation.

[138]  Anne J. Ridley,et al.  Shear stress–induced endothelial cell polarization is mediated by Rho and Rac but not Cdc42 or PI 3-kinases , 2003, The Journal of cell biology.

[139]  T. Peterson,et al.  MAP kinase activation by flow in endothelial cells. Role of beta 1 integrins and tyrosine kinases. , 1996, Circulation research.

[140]  M. Takeichi,et al.  p60v‐src causes tyrosine phosphorylation and inactivation of the N‐cadherin‐catenin cell adhesion system. , 1993, The EMBO journal.

[141]  K. Burridge,et al.  P120 Catenin Regulates the Actin Cytoskeleton via Rho Family Gtpases , 2000, The Journal of cell biology.

[142]  D. Tsuruta,et al.  The vimentin cytoskeleton regulates focal contact size and adhesion of endothelial cells subjected to shear stress , 2003, Journal of Cell Science.

[143]  D. Lauffenburger,et al.  Cell Migration: A Physically Integrated Molecular Process , 1996, Cell.

[144]  Shu Chien,et al.  The role of the dynamics of focal adhesion kinase in the mechanotaxis of endothelial cells , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[145]  C. Dewey Effects of fluid flow on living vascular cells. , 1984, Journal of biomechanical engineering.

[146]  Amit Kumar Sharma,et al.  Crystal structure of a heparin‐ and integrin‐binding segment of human fibronectin , 1999, The EMBO journal.

[147]  C. Mineo,et al.  Polarized Distribution of Endogenous Rac1 and RhoA at the Cell Surface* , 1999, Journal of Biological Chemistry.

[148]  Richard O. Hynes,et al.  Integrin-mediated Signals Regulated by Members of the Rho Family of GTPases , 1998, The Journal of cell biology.

[149]  S. Bagrodia,et al.  Cytoskeletal Reorganization by G Protein-Coupled Receptors Is Dependent on Phosphoinositide 3-Kinase γ, a Rac Guanosine Exchange Factor, and Rac , 1998, Molecular and Cellular Biology.

[150]  J. Palmaz,et al.  Human aortic endothelial cell migration onto stent surfaces under static and flow conditions. , 1997, Journal of vascular and interventional radiology : JVIR.

[151]  G M Bokoch,et al.  Activation of Rac and Cdc42 by integrins mediates cell spreading. , 1998, Molecular biology of the cell.

[152]  L. Van Aelst,et al.  Rho GTPases and signaling networks. , 1997, Genes & development.

[153]  A. Woods,et al.  Syndecans: synergistic activators of cell adhesion. , 1998, Trends in cell biology.

[154]  C F Dewey,et al.  Shear stress gradients remodel endothelial monolayers in vitro via a cell proliferation-migration-loss cycle. , 1997, Arteriosclerosis, thrombosis, and vascular biology.

[155]  A. Harris,et al.  Silicone rubber substrata: a new wrinkle in the study of cell locomotion. , 1980, Science.

[156]  Yoshimi Takai,et al.  Induction of filopodium formation by a WASP-related actin-depolymerizing protein N-WASP , 1998, Nature.

[157]  E. Ruoslahti,et al.  Tyrosine Phosphorylation of p130Cas and Cortactin Accompanies Integrin-mediated Cell Adhesion to Extracellular Matrix (*) , 1995, The Journal of Biological Chemistry.

[158]  Kayla J Bayless,et al.  Molecular basis of endothelial cell morphogenesis in three‐dimensional extracellular matrices , 2002, The Anatomical record.

[159]  A. Horwitz,et al.  Integrin cytoplasmic domains: mediators of cytoskeletal linkages and extra- and intracellular initiated transmembrane signaling. , 1993, Current opinion in cell biology.

[160]  M. Lampugnani,et al.  The Role of Endothelial Cell-to-Cell Junctions in Vascular Morphogenesis , 1999, Thrombosis and Haemostasis.

[161]  D. Paul,et al.  Connexin43 is highly localized to sites of disturbed flow in rat aortic endothelium but connexin37 and connexin40 are more uniformly distributed. , 1998, Circulation research.

[162]  S Chien,et al.  Shear stress induces spatial reorganization of the endothelial cell cytoskeleton. , 1998, Cell motility and the cytoskeleton.

[163]  R. Hynes,et al.  Syndecan-4 signals cooperatively with integrins in a Rho-dependent manner in the assembly of focal adhesions and actin stress fibers. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[164]  V. Sah,et al.  The role of Rho in G protein-coupled receptor signal transduction. , 2000, Annual review of pharmacology and toxicology.

[165]  M. Corada,et al.  VE-cadherin regulates endothelial actin activating Rac and increasing membrane association of Tiam. , 2002, Molecular biology of the cell.

[166]  S. Nishikawa,et al.  WAVE2 is required for directed cell migration and cardiovascular development , 2003, Nature.

[167]  B A Danowski,et al.  Fibroblast contractility and actin organization are stimulated by microtubule inhibitors. , 1989, Journal of cell science.

[168]  R. Nerem,et al.  Endothelial cell signaling and cytoskeletal changes in response to shear stress. , 1993, Frontiers of medical and biological engineering : the international journal of the Japan Society of Medical Electronics and Biological Engineering.

[169]  C. Fiorentini,et al.  Dissection of Pathways Implicated in Integrin-mediated Actin Cytoskeleton Assembly , 1997, The Journal of Biological Chemistry.

[170]  D E Ingber,et al.  Mechanotransduction across the cell surface and through the cytoskeleton. , 1993, Science.

[171]  M. Lampugnani,et al.  The role of integrins in the maintenance of endothelial monolayer integrity , 1991, The Journal of cell biology.

[172]  D. Gingras,et al.  Localization of RhoA GTPase to endothelial caveolae-enriched membrane domains. , 1998, Biochemical and biophysical research communications.

[173]  F. Giancotti,et al.  The Adaptor Protein Shc Couples a Class of Integrins to the Control of Cell Cycle Progression , 1996, Cell.

[174]  Kenneth M. Yamada,et al.  Site-directed mutagenesis of the cell-binding domain of human fibronectin: Separable, synergistic sites mediate adhesive function , 1988, Cell.

[175]  M. Sheetz,et al.  A micromachined device provides a new bend on fibroblast traction forces. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[176]  John G. Collard,et al.  Rac Downregulates Rho Activity: Reciprocal Balance between Both Gtpases Determines Cellular Morphology and Migratory Behavior , 1999 .

[177]  信司 大久保 虚血耐性の機序における tyrosine phosphorylation の役割 , 2003 .

[178]  R. Assoian,et al.  Integrin-dependent activation of MAP kinase: a link to shape-dependent cell proliferation. , 1995, Molecular biology of the cell.

[179]  Luft Jh Fine structures of capillary and endocapillary layer as revealed by ruthenium red. , 1966 .

[180]  A Ratcliffe,et al.  Effects of flow patterns on endothelial cell migration into a zone of mechanical denudation. , 2001, Biochemical and biophysical research communications.

[181]  M. Broman,et al.  Cdc42 Regulates the Restoration of Endothelial Barrier Function , 2004, Circulation research.

[182]  Richard G. W. Anderson,et al.  Integrins Regulate Rac Targeting by Internalization of Membrane Domains , 2004, Science.

[183]  B. Duling,et al.  Identification of distinct luminal domains for macromolecules, erythrocytes, and leukocytes within mammalian capillaries. , 1996, Circulation research.

[184]  S. Chien,et al.  Activation of Rac1 by shear stress in endothelial cells mediates both cytoskeletal reorganization and effects on gene expression , 2002, The EMBO journal.

[185]  Brian P Helmke,et al.  Spatial microstimuli in endothelial mechanosignaling. , 2003, Circulation research.

[186]  J. Frangos,et al.  Fluid flow rapidly activates G proteins in human endothelial cells. Involvement of G proteins in mechanochemical signal transduction. , 1996, Circulation research.

[187]  A. Woods,et al.  Syndecan 4 heparan sulfate proteoglycan is a selectively enriched and widespread focal adhesion component. , 1994, Molecular biology of the cell.

[188]  S. Aota,et al.  The short amino acid sequence Pro-His-Ser-Arg-Asn in human fibronectin enhances cell-adhesive function. , 1994, The Journal of biological chemistry.

[189]  S. Aizawa,et al.  Reduced cell motility and enhanced focal adhesion contact formation in cells from FAK-deficient mice , 1995, Nature.

[190]  S. Chien,et al.  Roles of Microtubule Dynamics and Small GTPase Rac in Endothelial Cell Migration and Lamellipodium Formation under Flow , 2002, Journal of Vascular Research.

[191]  John G. Collard,et al.  Reactive oxygen species mediate Rac-induced loss of cell-cell adhesion in primary human endothelial cells. , 2002, Journal of cell science.

[192]  Luke P. Lee,et al.  Role of cell surface heparan sulfate proteoglycans in endothelial cell migration and mechanotransduction , 2005, Journal of cellular physiology.

[193]  S. Miyamoto,et al.  Initiation and Transduction of Stretch-induced RhoA and Rac1 Activation through Caveolae , 2003, Journal of Biological Chemistry.

[194]  Elisabetta Dejana,et al.  VEGF receptor 2 and the adherens junction as a mechanical transducer in vascular endothelial cells , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[195]  N Harbeck,et al.  Spatial and temporal regulation of gap junction connexin43 in vascular endothelial cells exposed to controlled disturbed flows in vitro. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[196]  Richard O. Hynes,et al.  Integrins: Versatility, modulation, and signaling in cell adhesion , 1992, Cell.

[197]  Feng Xu,et al.  Assembly and reorientation of stress fibers drives morphological changes to endothelial cells exposed to shear stress. , 2004, The American journal of pathology.

[198]  J H Hartwig,et al.  Gelsolin is a downstream effector of rac for fibroblast motility , 1998, The EMBO journal.

[199]  R. Goldman,et al.  Rapid displacement of vimentin intermediate filaments in living endothelial cells exposed to flow. , 2000, Circulation research.