Matrix Mechanics and Cell Contractility in Angiogenesis - Mechanical and Chemical Signaling in Angiogenesis - page 142

Fig. 1 Changes in cell shape accompany alterations in focal adhesion formation and cell
contractility. a Endothelial cells cultured on square micropatterned adhesive islands were used to
determine the role of shape on focal adhesion formation (clockwise from top left, the square side
lengths are 10, 40, 5, and 20 lm, respectively. b The number of vinculin- (a focal adhesion
protein required for normal cell spreading [ 30 ]), and phosphotyrosine- (PTyr, a marker for
tyrosine kinase signaling) positive focal adhesions increases with increasing spread size (from
[ 15 ] with permission). c EC spreading and traction force generation increase with increasing
substrate stiffness. Cells exhibit bipolar spreading on compliant (E = 1 kPa) matrices and
increase spreading as stiffness is increased. The total magnitude of the traction stress T also
increases with increasing substrate stiffness (from [ 13 ] with permission)

plasma membrane [ 14 ]. When ECs spread, there is an increase in focal adhesion
density that increases with the degree of cell spreading [ 15 ] (Fig. 1 a, b).
Focal adhesion assembly is also sensitive to cell contractility and cell-cell
interactions [ 15 , 16 ]. Increased endothelial cell-cell contact decreases cell
spreading and the size and number of focal adhesions [ 17 ]. However, Nelson et al.
showed that when cells are patterned to be in contact, but changes in spreading are
prevented, focal adhesion formation increases. These changes result from
VE-cadherin-mediated increases in cytoskeletal tension (increasing RhoA activity)
that increases focal adhesion formation. Similar to integrin-mediated contractility,
cadherin-mediated increases in contractility are actin-dependent. Interestingly,
cadherins have been shown to transmit traction forces [ 18 , 19 ] that increase with
increasing substrate stiffness, and require actin cytoskeletal assembly and myosin
activity

[ 20 ]. Furthermore, changes in Rho-mediated contractility influence