Epithelial cells cultured on type I collagen gels adopt a typical apical—basal polarity and undergo differentiation. We have compared the behaviour of chick embryo retinal pigmented epithelial (RPE) cells on collagen and on plastic with and without gelatin coats. RPE cell proliferation was similar on all three substrata, and post-confluent cultures exhibited multilayering. On plastic and gelatin-coated plastic, dome formation, typical of transporting epithelia, occurred. On type I collagen gels, however, dome formation did not occur, but rather invasion of the gel matrix by cords of epithelial cells took place. In contrast, invasive behaviour of the cells was markedly reduced on type IV coated collagen gels, particularly in the presence of laminin. These results illustrate the prominent role of the extracellular matrix on phenotypic expression by RPE cells and may represent a more general phenomenon.

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