GROWTH INHIBITION OF HUMAN FIBROBLASTS BY RECONSTITUTED COLLAGEN FIBRILS

Abstract

Experiments with fibroblasts in culture demonstrated that collagen fibrilsstrongly inhibited DNA synthesis, and suppressed cell growth. Collagen fibrils also induced a specific cell shape with abundant cytoplasmic protrusions. The rate of DNA synthesis on collagen was less than 20% of that on tissue culture plastic. The extent of the suppression of DNA synthesis was strictly dependent upon the quantity of collagen available to cells. 60 pg/cell, which differed from that for the induction of a collagen-mediated change in the cell shape (5.3 ng/cell). The extent of suppression of DNA synthesis on collagen fibrils decreased as the length of culture period increased, suggesting that fibroblasts interact with collagen during culture and induce changes in the properties of collagen. Native collagen which loses ability to form a fibril in the culture condition was prepared by modifying ε-amino groups of lysyl residues. The chemically modified collagen didnot induce any collagen-mediated changes in fibroblasts, indicating the importance of a polymeric form of collagen for collagen to cell interaction.