Blood-clotting proteins, interaction with surfaces

This study deals with the formation of complexes between blood clotting proteins and natural and artificial surfaces. As these surfaces are generally charged, the behavior of a basic protein, cardiotoxin (CTX), the interaction of which is strictly charge-dependent, is also reported for comparison. Two types of interface have been investigated. 

At least three other families of plasma membrane proteins are also involved in surface adhesion (Fig. 11-22). Cadherins undergo homophilic ( with same kind ) interactions with identical cadherins in an adjacent cell. Immunoglobulin-like proteins can undergo either homophilic interactions with their identical counterparts on another cell or heterophilic interactions with an integrin on a neighboring cell. Selectins have extracellular domains that, in the presence of Ca2+, bind specific polysaccharides on the surface of an adjacent cell. Selectins are present primarily in the various types of blood cells and in the endothelial cells that line blood vessels (see Fig. 7-33). They are an essential part of the blood-clotting process. 

The induction of a change in one protein by interaction with another protein is a phenomenon that is met also in the construction of microtubules, ribosomes, cilia, and myofibrillar assemblies of muscle. It is basic to the assembly of the many labile but equally real cascade systems of protein-protein interactions such as that involved in the clotting of blood (Chapter 12) and signaling at membrane surfaces. 

Following the recruitment and activation of platelets by injured capillaries, their soft clot aggregates provide a surface for plasma proteins to interact and activate thrombin, which transforms soluble fibrinogen to a fibrin clot. Thrombin is activated by two blood coagulation pathways, extrinsic and intrinsic. A defective extrinsic path is incompatible with life, whereas defects of the intrinsic path cause hemophilia. 

The adsorption of proteins is the first interaction which occurs when a foreign surface comes in contact with blood. The processes which then lead to hemostasis are attachment of cellular elements to the surface, platelet adhesion and release, and triggering of the blood coagulation cascade. Investigations of interactions of proteins at the interface, which are the primary steps in blood clotting and determine whether it will occur, are hence of fundamental importance. 

Blood-surface interactions are of great importance when medical polymers, such as those used in heart valves and artificial organs, are implanted into the body. When polymers come into contact with blood, complex reactions take place and can result in the formation of a blood clot. Infrared analysis has shown in ex vivo studies that during the early stages the proteins albnmin and glycoprotein are present, with fibronogen subsequently appearing. As the adsorption process continues, albumin is replaced by other proteins until a blood clot is formed. 

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