Determination of cellular shape by the extracellular matrix and its correlation with the control of cellular growth

Although the problem of cellular proliferation may seem at first glance to be tremendously complex, the mechanisms which control it may be extremely simple. One of the primary factors which regulates the mitogenic response of a given cell type to a given class of mitogenic agents seems to be the cellular shape. We have found that corneal epithelial cells, for example, adopt a flattened configuration when maintained in vitro on plastic and are very sensitive to fibroblast growth factor, but not to epidermal growth factor. When maintained on collagen, on the other hand, they become tall and columnar and respond primarily to epidermal growth factor. The cellular shape is dictated in vivo by the extracellular material upon which the cells rest and in vitro by the substrate upon which the cells are maintained. The substrate itself may, in turn, induce the cells to manufacture their extracellular material and specific cell surface proteins which control the cellular shape.