Physiological variables affecting collagen lattice contraction by human dermal fibroblasts.
Normal human dermal fibroblasts cultured in collagen lattices can compact that matrix by the process known as lattice contraction. That process is a model of the pathological one of scar contracture or wound contraction and is affected by several factors. Lattice contraction is promoted by the addition of adequate amounts of fetal bovine serum to the medium (maximum contraction with 10% serum). The process requires energy, of which glucose and pyruvate have been shown to be adequate sources. When glucose is used as the substrate, the major pathway of energy generation appears to be anaerobic metabolism. When pyruvate is the only substrate, aerobic metabolism may be crucial. The synthesis of DNA is not required for lattice contraction, while protein synthesis is, although the identities of the specific proteins are unknown. Impairment of calcium ion transport inhibits lattice contraction, and the specific inhibition of calmodulin-calcium interactions by W-7 blocks contraction. W-7 at a concentration of 6 x 10(-6) M blocks lattice contraction completely, while it has no effect at any lower concentration. Impairing dynamic microtubule activity impairs contraction. Disrupting microfilaments by cytochalasin B completely blocks lattice contraction. Microfilament function and calcium-calmodulin may be linked by a mechanism involving myosin-ATPase. The process of cell-mediated lattice contraction requires the production of energy, protein synthesis, and a functional cytoskeleton.
Ehrlich
H P
HP
Shriners Burns Institute, Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston 02114.
Buttle
D J
DJ
Bernanke
D H
DH
D002118:Calcium / Q000493:pharmacokinetics; D003094:Collagen / Q000378:metabolism / Q000502:physiology*; D003599:Cytoskeleton / Q000502:physiology; D004247:DNA / Q000096:biosynthesis; D000078404:Epidermal Cells; D005260:Female; D005347:Fibroblasts / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D011506:Proteins / Q000378:metabolism
D011506:Proteins; D003094:Collagen; D004247:DNA; D002118:Calcium