Thesis

Molecular cell adhesion modeling using nucleotide and carbohydrate derivatized beaded agarose resin

Cell adhesion has been studied for almost a century beginning with H.V. Wilson's classic studies on sponge cell aggregation. Cell adhesion plays an important role in morphogenesis and malignancy, but its molecular basis is poorly understood. As the cell surface often consists of hundreds of different molecules, it has been difficult to identify those molecular groups that function in the specific adhesion that occurs between cells. Students in this laboratory have approached this problem in a novel way. By examining the adhesion of agarose beads derivatized with only one type of molecule, one can learn more about which molecules, when isolated from all others, can adhere and which cannot, under conditions of the assay. Approximately 20,000 molecular combinations are being tested for adhesion in this laboratory. This thesis describes the work on 570 combinations of nucleotides and carbohydrates, each repeated at least three times. Although there is no evidence that interactions of these molecules are involved in cell adhesion, or even that nucleotides commonly occur on cell surfaces, it was important to examine all available molecular combinations because they may offer clues about the types of bonds that can form stable adhesions. For example, if nucleotides and carbohydrates adhered to each other via hydrogen bonding, this would provide evidence that hydrogen bonding can mediate adhesion. Fifteen different nucleotide derivatized beads were crossed with thirty-eight different carbohydrate derivatized beads and examined for adhesion to each other in distilled water and artificial sea water. All combinations that displayed any positive adhesion were repeated by at least two individuals. All 570 bead combinations did not adhere under the conditions of the assay, indicating that this set of nucleotides and carbohydrates did not form bonds stable enough to hold cell sized particles together. Previous experiments in the lab have shown that certain bead combinations could adhere under these conditions, leading to hypotheses concerning adhesion mechanisms that are being tested in living systems (Acta histochemica 98:441-451, 1996). The negative results presented in this study are meaningful in improving our understanding of what types of molecules can or cannot form stable bonds in a cell-like model system that allows the study of isolated molecular combinations.

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