Basic mechanism of three-dimensional collagen fibre transport by fibroblasts

Adam S. Meshel, Qize Wei, Robert S. Adelstein, Michael Sheetz

Research output: Contribution to journalArticle

206 Citations (Scopus)

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 α2β1 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.

Original languageEnglish (US)
Pages (from-to)157-164
Number of pages8
JournalNature Cell Biology
Volume7
Issue number2
DOIs
StatePublished - Feb 1 2005
Externally publishedYes

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Nonmuscle Myosin Type IIB
Myosin Type II
Collagen
Fibroblasts
Hand
Pseudopodia
Green Fluorescent Proteins
Integrins
Cell Movement
Gels

ASJC Scopus subject areas

  • Cell Biology

Cite this

Basic mechanism of three-dimensional collagen fibre transport by fibroblasts. / Meshel, Adam S.; Wei, Qize; Adelstein, Robert S.; Sheetz, Michael.

In: Nature Cell Biology, Vol. 7, No. 2, 01.02.2005, p. 157-164.

Research output: Contribution to journalArticle

Meshel, Adam S. ; Wei, Qize ; Adelstein, Robert S. ; Sheetz, Michael. / Basic mechanism of three-dimensional collagen fibre transport by fibroblasts. In: Nature Cell Biology. 2005 ; Vol. 7, No. 2. pp. 157-164.
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