New research published today in the Journal of Cell Biology illuminates the mechanical factors that play a critical role in the differentiation and function of fibroblasts, connective tissue cells that play a role in wound healing and scar tissue formation.
When we are injured, the body launches a complex rescue operation. Specialized cells called fibroblasts lurking just beneath the surface of the skin jump into action, enter the provisional wound matrix (the clot) and start secreting collagen to close the wound as fast as possible. This matrix is initially soft and loaded with growth factors. The fibroblasts "crawl" around the matrix, pulling and reorganizing the fibers. The matrix grows stiffer, and at a certain point, the fibroblasts stop migrating and, like Popeye, change into powerful contractile cells, anchoring themselves to the matrix and pulling the edges of the wound together.
The research reported today reveals for the first time that a mechanical mechanism is crucial for this switch from migrating to contractile cells. To make this change, the fibroblasts need to get at their "spinach" -- the growth factor sitting in the matrix which, once liberated, stimulates the production of smooth-muscle proteins. Previously, researchers postulated that the fibroblasts did this by digesting the matrix. But EPFL scientist Boris Hinz, doctoral student Pierre-Jean Wipff and their colleagues have discovered that the cells unlock the growth factor via a purely mechanical process. With experiments using novel cell culture substrates of varying rigidity, they found that at a certain point, the matrix is sufficiently rigid that cell-exerted force allows the growth factor to pop out, like candy from a wrapper. Once the growth factor is available, the fibroblast expresses the contractile proteins, sticks more firmly to the matrix and starts to contract, pulling the matrix tightly together. In the process it liberates yet more growth factor that in turn stimulates other fibroblasts to become contractile. The mechanical nature of the switch ensures that the contraction only develops when the matrix is "ready."