Basic mechanism of three-dimensional collagen fibre transport by fibroblasts
- Nat Cell Biol. 2005 Feb;7(2):157-64. doi: 10.1038/ncb1216.
- 1. Department of Biological Sciences, Columbia University, New York, NY 10027, USA.
Collagen remodelling by fibroblasts has a crucial role in organizing tissue structures that are essential to motility during wound repair, development and regulation of cell growth. However, the mechanism of Collagen fibre movement in three-dimensional (3D) matrices is not understood. Here, we show that fibroblast lamellipodia extend along held Collagen fibres, bind, and retract them in a 'hand-over-hand' cycle, involving alpha2beta1 Integrin. Wild-type fibroblasts move Collagen fibres three to four times farther per cycle than fibroblasts lacking Myosin II-B (Myosin II-B(-/-)). Similarly, Myosin II-B(-/-) fibroblasts contract 3D Collagen gels threefold less than controls. On two-dimensional (2D) substrates, however, rates of Collagen bead and cell movement are not affected by loss of Myosin II-B. Green fluorescent protein (GFP)-tagged Myosin II-B, but not II-A, restores normal function in knockout cells and localizes to cell processes, whereas Myosin II-A is more centrally located. Additionally, GFP-myosin II-B moves out to the periphery and back during hand-over-hand fibre movement, whereas on 2D Collagen, Myosin II-B is more centrally distributed. Thus, we suggest that cyclic Myosin II-B assembly and contraction in lamellipodia power 3D fibre movements.