LPA-stimulated fibroblast contraction of floating collagen matrices does not require Rho kinase activity or retraction of fibroblast extensions

Fibroblasts synthesize, organize, and maintain connective tissues during development and in response to injury and fibrotic disease. These morphogenetic processes depend on cell-matrix remodeling, which has been investigated using cells cultured in three-dimensional collagen matrices. The current studies were carried out to test the role of Rho kinase activity and retraction of fibroblast extensions on the matrix remodeling process. We found that remodeling (contraction) of floating collagen matrices stimulated by lysophosphatidic acid (LPA) did not require Rho kinase activity or retraction of fibroblast extensions. On the other hand, LPA-stimulated contraction of restrained matrices became Rho kinase dependent after the matrices were allowed to develop mechanical loading for 2-4 h, suggesting that the remodeling process itself was able to feed back to modulate cell behavior in an iterative process. Modulation was specific for LPA since fibroblast-collagen matrix contraction stimulated by platelet-derived growth factor was Rho kinase dependent before or after mechanical loading developed.