Localized differences in cell proliferation can help sculpt tissues during morphogenesis and produce the complex structures found in mature organisms. In some cases, however, changes in tissue structure occur before changes in cell proliferation. To show that geometry could itself feed back and regulate cell proliferation, Nelson et al.cultured bovine pulmonary artery endothelial cells on small fibronectin-coated islands surrounded by nonadhesive regions. Examination of cell growth on islands of different sizes and shapes—or on undulating surfaces—revealed distinctive and nonuniform patterns of proliferation. A finite element model predicted that cell proliferation would be greatest in regions of high mechanical stress; this was confirmed by culturing cells on a force sensor array that allowed traction forces to be measured directly. Pharmacological inhibition of Rho kinase, myosin light-chain kinase, or nonmuscle myosin II ATPase (to decrease tension generated through the cytoskeleton), or disruption of cadherin-mediated intercellular adhesions, attenuated gradients of cell proliferation, whereas expression of a constitutively active RhoA mutant enhanced them. — EMA
Proc. Natl. Acad. Sci. U.S.A. 102, 11594 (2005).