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Effect of reconstituted type I collagen gel on in vitro growth of fibroblasts was examined. A prolonged lag period was observed by culture either on the surface of three-dimensional collagen gel ("on-gel") or within the gels ("in-gel") as compared with the culture on plastic dishes. The rate of cell proliferation in logarithmic phase growth was repressed by the culture "in-gel" but not by the culture "on-gel". The differential growth rates between "in-gel" culture and "on-gel" culture should be ascribed to difference in distributions of interacting sites between cell and collagen fibrils. The repression of cell growth was more marked in a contracting collagen gel which contains higher density of collagen fibrils. The cell density in contracted gel per unit cross-section area was found to be much lower than that of confluent monolayer culture. These results suggest that the repression of cell growth by collagen fibrils in the three-dimensional gels is not due to direct cell-cell contact, but due to the distribution and number of contact sites between a cell and collagen fibrils.
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