Mechanotransduction by Endothelial Cells Is Locally Generated, Direction-Dependent, and Ligand-Specific

被引:29
作者
Chretien, Marc L. [1 ,2 ]
Zhang, Ming [2 ]
Jackson, Moira R. [3 ]
Kapus, Andras [4 ]
Langille, B. Lowell [1 ,2 ]
机构
[1] Univ Toronto, Dept Lab Med & Pathobiol, Toronto, ON M5S 1A8, Canada
[2] Univ Hlth Network, Toronto Gen Res Inst, Toronto, ON MSG 2C4, Canada
[3] Univ Florida, Coll Med, Dept Anat & Cell Biol, Gainesville, FL 32610 USA
[4] Univ Toronto, St Michaels Hosp, Li Ka Sheng Knowledge Inst, Keenan Res Ctr,Dept Surg, Toronto, ON M5B 1W8, Canada
关键词
FLUID SHEAR-STRESS; ACTIVATED PROTEIN-KINASE; SMOOTH-MUSCLE-CELLS; ADHESION MOLECULE-1; VASCULAR ENDOTHELIUM; SIGNALING PATHWAYS; NITRIC-OXIDE; FORCE; AKT; PHOSPHORYLATION;
D O I
10.1002/jcp.22125
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Vascular endothelial cells display a wide panel of responses to changes in the shear stress that is exerted on them by blood flow. How sensory mechanisms convey information about flow conditions and how this information is integrated remains poorly understood. The issue is confounded by: (1) a large number of potential force sensors, (2) difficulties in differentiating these sensors from downstream sites of signal integration, and (3) the complexities inherent in understanding how forces are transmitted from the apical surface of the cell via the cytoskeleton to intracellular sites. As a consequence, neither the structures that sense force nor the nature of the forces that loads them have been clearly defined. In this study, we employed magnetic microspheres coated with ligands that bind integrin subsets (RGD peptides or type I collagen) or PECAM-1 to discriminate the downstream signaling effects of different sensor molecules and mechanisms for how they are loaded. We found that application of force to these transmembrane molecules elicited biologically important signaling (ERK1/2, AKT, and GSK-3 beta phosphorylation), and downstream biological responses that depended on the following two factors: (1) the ligand that transmitted force and (2) the direction in which force was applied. These findings indicate that ligands locally generate different shear-induced responses in endothelium that depend on how force is delivered. J. Cell. Physiol. 224: 352-361, 2010. (C) 2010 Wiley-Liss, Inc.
引用
收藏
页码:352 / 361
页数:10
相关论文
共 42 条
[1]  
ALENGHAT FJ, 2002, SCI STKE, V119, pE6
[2]   SUBCELLULAR-DISTRIBUTION OF SHEAR-STRESS AT THE SURFACE OF FLOW-ALIGNED AND NONALIGNED ENDOTHELIAL MONOLAYERS [J].
BARBEE, KA ;
MUNDEL, T ;
LAL, R ;
DAVIES, PF .
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY, 1995, 268 (04) :H1765-H1772
[3]   SHEAR STRESS-INDUCED REORGANIZATION OF THE SURFACE-TOPOGRAPHY OF LIVING ENDOTHELIAL-CELLS IMAGED BY ATOMIC-FORCE MICROSCOPY [J].
BARBEE, KA ;
DAVIES, PF ;
LAL, R .
CIRCULATION RESEARCH, 1994, 74 (01) :163-171
[4]  
CHRETIEN M, 2006, HEMOSTATSIS THROMBOS, P667
[5]   Force-induced polarized mitosis of endothelial and smooth muscle cells in arterial remodeling [J].
Dajnowiec, Dorota ;
Sabatini, Peter J. B. ;
Van Rossum, Thea C. ;
Lam, Jacky T. K. ;
Zhang, Ming ;
Kapus, Andras ;
Langille, B. Lowell .
HYPERTENSION, 2007, 50 (01) :255-260
[6]   Akt phosphorylation of BAD couples survival signals to the cell-intrinsic death machinery [J].
Datta, SR ;
Dudek, H ;
Tao, X ;
Masters, S ;
Fu, HA ;
Gotoh, Y ;
Greenberg, ME .
CELL, 1997, 91 (02) :231-241
[7]   FLOW-MEDIATED ENDOTHELIAL MECHANOTRANSDUCTION [J].
DAVIES, PF .
PHYSIOLOGICAL REVIEWS, 1995, 75 (03) :519-560
[8]   Integrins and mechanotransduction of the vascular myogenic response [J].
Davis, MJ ;
Wu, X ;
Nurkiewicz, TR ;
Kawasaki, J ;
Davis, GE ;
Hill, MA ;
Meininger, GA .
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY, 2001, 280 (04) :H1427-H1433
[9]   Stretching Single Talin Rod Molecules Activates Vinculin Binding [J].
del Rio, Armando ;
Perez-Jimenez, Raul ;
Liu, Ruchuan ;
Roca-Cusachs, Pere ;
Fernandez, Julio M. ;
Sheetz, Michael P. .
SCIENCE, 2009, 323 (5914) :638-641
[10]   Localized mechanical stress induces time-dependent actin cytoskeletal remodeling and stiffening in cultured airway smooth muscle cells [J].
Deng, LH ;
Fairbank, NJ ;
Fabry, B ;
Smith, PG ;
Maksym, GN .
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY, 2004, 287 (02) :C440-C448