The different roles of myosin IIA and myosin IIB in contraction of 3D collagen matrices by human fibroblasts

• We tested the role of myosin II isoforms in fibroblast interactions with 3D collagen matrices.
• MyoIIA was required for stressed matrix contraction and morphogenic cell clustering.
• Either MyoIIA or MyoIIB was sufficient for PDGF-floating matrix contraction.
• Neither MyoIIA or MyoIIB was necessary for serum-floatin matrix contraction.
• Motor mechanisms for collagen contraction depend on cell tension and growth factor stimulation.

Contraction of 3D collagen matrices by fibroblasts frequently is used as an in vitro model of wound closure. Different iterations of the model – all conventionally referred to as “contraction” – involve different morphological patterns. During floating matrix contraction, cells initially are round without stress fibers and subsequently undergo spreading. During stressed matrix contraction, cells initially are spread with stress fibers and subsequently undergo shortening. In the current studies, we used siRNA silencing of myosin IIA (MyoIIA) and myosin IIB (MyoIIB) to test the roles of myosin II isoforms in fibroblast interactions with 3D collagen matrices and collagen matrix contraction. We found that MyoIIA but not MyoIIB was required for cellular global inward contractile force, formation of actin stress fibers, and morphogenic cell clustering. Stressed matrix contraction required MyoIIA but not MyoIIB. Either MyoIIA or MyoIIB was sufficient for floating matrix contraction (FMC) stimulated by platelet-derived growth factor. Neither MyoIIA or MyoIIB was necessary for FMC stimulated by serum. Our findings suggest that myosin II-dependent motor mechanisms for collagen translocation during extracellular matrix remodeling differ depending on cell tension and growth factor stimulation.