Cell coupling modulates the contraction of fibroblast-populated collagen lattices.

Abstract

Cultured dermal fibroblasts become notably elongated when incorporated into a fibroblast-populated collagen lattice (FPCL). With time these fibroblasts reorganize the collagen responsible for reduction in lattice size. In monolayer the microinjection of Lucifer Yellow (LY) into cultured human fibroblasts shows cell coupling through gap junctions. Human fibroblasts residing on the periphery of a FPCL are at high density and the microinjection of LY into one of those fibroblasts demonstrates cell coupling. Cells within the center of an FPCL are at low density and appear to be independent of one another; however, the microinjection of LY into selected fibroblasts again demonstrates cell coupling. Hence the microinjection of cells in both the center and the edge of a FPCL pass dye to numerous neighbors. Does cell coupling influence FPCL contraction? FPCL incubated with heptanol and octanol, aliphatic alcohols that uncouple cells, inhibits lattice contraction, whereas hexanol, an aliphatic alcohol that does not uncouple cells, did not alter lattice contraction. Fibroblasts derived from connexin 43 (a transmembrane protein responsible for gap junction structures) knockout mice were demonstrated to lack gap junctional communications. When incorporated into a FPCL these cells failed to elongate and demonstrated retarded lattice contraction. Hence, gap junctional communications between fibroblasts incorporated into collagen lattices appear to optimize FPCL contraction and suggest a role for gap junctions in the organization of collagen fibers.