Cell-substratum interactions and the cytoskeleton in cell shape-mediated growth regulation of lens epithelial cells.

Cell attachment to a suitable substratum is a precondition for the mitotic growth of nontransformed lens epithelial cells. Cultering of cells in suspension results in a strong decline of the DNA synthetic rate, whereas reattachment induces the reentrance into the cell cycle. Further studies revealed that not anchorage itself but cell flattening is prerequisite for the entrance of cells into the cycle. Flattened cells exert tension to the substratum via numerous filopodia. If the rigidity of the substratum is reduced by loosening of the collagen gel from the bottom of the petri dish, the gel becomes contracted by the traction forces of the cells and the cell shape becomes transformed from a flattened shape into a more spheroidal or longstretched one. This cell shape transition is connected with a decrease in RNA- and protein synthesis and a stop of DNA synthesis. During further experiments it was demonstrated that microfilaments are involved in gel contraction and cell shape alteration, respectively. Furthermore, intact microfilaments are needed for G0-G1-S-transition. Desintegration of microfilaments by cytochalasin is without influence on ongoing DNA synthesis but hinders strongly the entrance of cells into the S-phase. The survey gives some recent results on the molecular basis of cell substratum interactions as well as the structure and function of the cytoskeleton. The role of the cytoskeleton in cell shape-mediated growth regulation is discussed.