MOLECULAR BASIS OF CELLULAR ADHESIVENESS

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Cellular adhesiveness is a fundamental feature of cell behavior. The long-term goal of my research is to determine the mechanisms underlying cell adhesion to extracellular substrata. During the next five years we intent to investigate several general features of adhesion that are poorly understood and to study relationships between fibronectin receptors and other cell surface binding sites involved in adhesion. Specific problems on which we will focus are as follows: (1) We have found that Mn-dependent attachment and spreading of baby hamster kidney (BHK) cells on culture dishes cannot be explained in terms of the generally accepted model of cell adhesion. We plan to determine the effects of Mn on bead binding and phagocytosis by BHK cells and to analyze the BHK cell components involved in Mn-dependent adhesion. (2) We plan to determine the specificity of removal of substratum-bound proteins from beneath focal adhesion sites during attachment and spreading of human fibroblasts and the possible importance of this substratum remodeling process in other aspects of cell behavior. (3) We recently have prepared monoclonal antibodies against the WGA sites of baby hamster kidney cells. Antibodies that appear to react with the 50kd and 140kd complex fibronectin receptors have been partially characterized and will be studied in greater detail. We plan to analyze the role of these receptors in cell adhesion to substrata other than fibronectin. (4) We have isolated a BHK cell variant defective in cell contact to Fn-coated culture dishes. We will determine whether the Fn receptors of these cells interact abnormally with the cytoskeleton and analyze other alterations in recruitment of cell components to sites of cell-substratum contact.