Fibroblasts regulate contractile force independent of MMP activity in 3D-collagen.
The extracellular matrix not only provides a structural scaffold for cells to inhabit but also forms a conduit by which mechanical information may be transmitted. Fibroblasts undergo a variety of changes when activated, including upregulating matrix metalloproteinase (MMP) activity and establishing a smooth muscle-like contractile apparatus. The relationship between MMP activity and matrix contraction has yet to be established. Here we report that inhibition of MMP activity correlates with a significant reduction in collagen gel contraction, however, force development does not change respective to MMP activity. These results suggest cellular controls of contractile forces are independent of MMP activity. Our results also raise the possibility that the material properties of the matrix dynamically change during remodeling.
Phillips
Jonathan A
JA
Department of Cell Biology, Center of Tissue Engineering, Graduate School of Biomedical Sciences, University of Massachusetts, Worcester, MA, USA.
Vacanti
Charles A
CA
Bonassar
Lawrence J
LJ
D000222:Adaptation, Physiological / Q000502:physiology; D000818:Animals; D002450:Cell Communication / Q000187:drug effects / Q000502:physiology; D002452:Cell Count; D018929:Cell Culture Techniques / Q000295:instrumentation / Q000379:methods*; D002478:Cells, Cultured; D024042:Collagen Type I / Q000502:physiology*; D003571:Cytochalasin B / Q000494:pharmacology; D004151:Dipeptides / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D005109:Extracellular Matrix / Q000187:drug effects / Q000502:physiology*; D005347:Fibroblasts / Q000187:drug effects / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D061965:Matrix Metalloproteinase Inhibitors; D020782:Matrix Metalloproteinases / Q000502:physiology*; D040542:Mechanotransduction, Cellular / Q000187:drug effects / Q000502:physiology*; D020409:Molecular Motor Proteins / Q000187:drug effects / Q000502:physiology*; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D051381:Rats; D013314:Stress, Mechanical
D024042:Collagen Type I; D004151:Dipeptides; D061965:Matrix Metalloproteinase Inhibitors; D020409:Molecular Motor Proteins; C078131:N-(2(R)-2-(hydroxamidocarbonylmethyl)-4-methylpentanoyl)-L-tryptophan methylamide; D003571:Cytochalasin B; D020782:Matrix Metalloproteinases