Cell-mediated remodeling and
wound closure are critical for efficient wound healing, but the contribution of
actin-binding proteins to contraction of the extracellular matrix is not defined. We examined the role of
filamin A (FLNa), an actin filament cross-linking
protein, in
wound contraction and maintenance of matrix tension. Conditional deletion of FLNa in fibroblasts in mice was associated with ~4 day delay of full-thickness skin
wound contraction compared with wild-type (WT) mice. We modeled the healing wound matrix using cultured fibroblasts plated on grid-supported
collagen gels that create lateral boundaries, which are analogues to
wound margins. In contrast to WT cells, FLNa knockdown (KD) cells could not completely maintain tension when matrix compaction was resisted by boundaries, which manifested as relaxed matrix tension. Similarly, WT cells on cross-linked
collagen, which requires higher levels of sustained tension, exhibited approximately fivefold larger deformation fields and approximately twofold greater fiber alignment compared with FLNa KD cells. Maintenance of boundary-resisted tension markedly influenced the elongation of cell extensions: in WT cells, the number (~50%) and length (~300%) of cell extensions were greater than FLNa KD cells. We conclude that FLNa is required for
wound contraction, in part by enabling elastic deformation and maintenance of tension in the matrix.