Basic mechanism of three-dimensional collagen fibre transport by fibroblasts

Nat Cell Biol. 2005 Feb;7(2):157-64. doi: 10.1038/ncb1216. Epub 2005 Jan 16.

Abstract

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Biological Transport
  • Cell Movement
  • Cells, Cultured
  • Collagen / metabolism*
  • Fibroblasts / metabolism*
  • Green Fluorescent Proteins
  • Integrin alpha2beta1 / metabolism
  • Mice
  • Nonmuscle Myosin Type IIA / metabolism
  • Nonmuscle Myosin Type IIB
  • Pseudopodia / metabolism
  • Time Factors

Substances

  • Integrin alpha2beta1
  • Green Fluorescent Proteins
  • Collagen
  • Nonmuscle Myosin Type IIA
  • Nonmuscle Myosin Type IIB