The role of cell shape for differentiation of choriocarcinoma cells on extracellular matrix.

The role of extracellular matrix (ECM) in directing cell differentiation has been interpreted so far predominantly in terms of chemical signaling from individual matrix molecules. Recent data, however, suggest that the physical properties of ECM contribute signals for differentiation, which can be decisive and possibly even more important than chemical composition. In the present investigation, effects of different artificial matrices on the differentiation of BeWo choriocarcinoma cells were studied systematically. In Series (a) cells were grown on nonspecifically adhesive substrate gels (gels of glyoxyl agarose with or without poly-L-lysine crosslinked to) and on artificial matrix gels (matrix molecules covalently bound to agarose gels). Differentiation in terms of chorionic gonadotropin (hCG) secretion was stimulated on all artificial gel substrates much more than on rigid substrates of the same chemical composition. Concomitantly a change in morphology was observed to a rounded shape of cells in aggregates attached to the substrate. A series (b) of substrates with gradually reduced adhesiveness was created by coating plastic with different concentrations of poly-HEMA. In this sequence, gradual changes in cell morphology (stepwise approximation to a spherical shape) correlated with increased hCG secretion comparable to that on matrix gels. In contrast, in aggregates kept in suspension the increase in secretion of hCG was only marginal. These results clearly support that in addition to chemical recognition of individual matrix molecules, cells respond strongly to physical properties of extracellular matrix and that the physics of interaction of cytoskeleton, cell surface, and ECM can become decisive for cell differentiation.