Fibroblast quiescence in floating or released collagen matrices: contribution of the ERK signaling pathway and actin cytoskeletal organization.

Fibroblasts in attached collagen matrices proliferate, whereas cells in floating or released matrices become quiescent. Cells in attached matrices had prominent actin stress fibers, indicating that they were under isometric tension, whereas stress fibers were absent from fibroblasts in floating or released matrices. Compared with cells in attached matrices, cells in floating or released matrices showed down-regulation of cyclin D1 and up-regulation of p27(Kip1) cyclin-dependent kinase inhibitor, and similar changes occurred after the ERK signaling pathway was blocked by UO126 in cells in attached matrices. A different pattern of changes in cell cycle regulatory proteins occurred, however, after serum deprivation or actin cytoskeletal depolymerization by latrunculin B, which did not prevent signaling through the ERK pathway. Therefore, cell quiescence in floating or released collagen matrices could be explained by decreased signaling through the ERK pathway, but these changes were not accounted for by the absence of isometric tension in the cells.