Protein-Protein Interactions Affecting Protein-Surface Interactions

Abstract: The focus of this thesis is the behaviour of proteins towards surfaces in the presence of other protein species. General protein-protein interactions of some plasma proteins are investigated in the first four papers. The proteins, immunoglobulin G, albumin, and fibrinogen, are analysed in solutions of single proteins as well as controlled mixtures. When introduced as a single species, proteins demonstrate certain interactions with respect to the free energy of a given surface. These interactions may vary remarkably if other proteins are introduced prior to the species under consideration, if they are co-incubated, or if other proteins are introduced following the adsorbed species. Some of these may be due to classical interactions such as competition and displacement while other may be due to co-operative, facilitative and non-competitive interactions or protein induced desorption. These are compared to protein behaviours of complex plasma protein mixtures found in blood plasma. The protein interactions are considered with regard to the hydrophobic/hydrophilic character of surfaces.The last two papers presented are concerned with protein-surface interactions that serve the fibrinolytic mechanism. Plasminogen binding to surfaces would prove invaluable in improving the fibrinolytic potential of biomaterial implants but in the past methods for selectively adsorbing plasminogen to surfaces other than fibrin coated surfaces have proved to be of limited success and resulted in no biomedical applications. Plasminogen binding surfaces consisting of lysinederivatised dextran layers were therefore studied. The kinetic mechanisms that lead to associations with the plasminogen binding surfaces are analysed and considered in light of current concepts of multisite plasminogen binding. The selectivity of plasminogen binding over other plasma proteins was investigated in consideration for a possible role of such surfaces in limiting and reversing the thrombic potential of biomaterials.

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