Interactions of fibrinolytic system proteins with lysine‐containing surfaces

Abstract

Studies on the interactions of tissue plasminogen activator (tPA) and plasminogen with polyurethane surfaces containing epsilon-lysine moieties (epsilon-amino group free) are reported. These surfaces are considered to have the potential to dissolve nascent clots that may be formed on them. For adsorption from both single protein solutions and plasma, the surfaces were found to have a high capacity for tPA as well as plasminogen. A significant fraction of preadsorbed tPA was displaced from the epsilon-lysine surfaces upon contact with plasma. These surfaces, when preadsorbed with tPA and then incubated with plasma, were able to dissolve incipient clots formed around them. However, the clot-dissolving capacity diminished as the time of plasma incubation increased, presumably due to loss of tPA. It was also shown that in plasma, preadsorbed tPA is displaced from these surfaces largely by plasminogen, which thus appears to have a greater binding affinity than tPA for the epsilon-lysine moieties. Finally, it was found that in plasma, the epsilon-lysine surfaces interact with plasminogen in a dynamic manner, and that about 70% of the bound plasminogen is exchanging continuously with plasminogen in the plasma.

ε-Aminocaproic Acid (EACA)

“…It does not inhibit synthetic substrate hydrolysis by plasminogen activators as well as hydrolysis synthetic substrate and protein degradation by plasmin. EACA binds to lysine binding sites (LBS) in plasminogen activators, plasminogen (free and in SK or SFK complex) and plasmin molecules (7, 8, The optimal distance between these groups is 0.68 nm (10). A decrease or an increase of this distance results in a reduction or a disappearance of antifibrinolytic activity (11,12).…”

Surface modification of biomaterials by photochemical immobilization and photograft polymerization to improve hemocompatibility

“…Moreover, plasminogen appeared to be bound to material surfaces in a way that facilitates its activation to plasmin by t-PA, similar to plasmin formation on the surface of fibrin. These surfaces were also demonstrated to have the ability of clot lysis and the potential to be fibrinolytic [43,44].…”

Mimicking the fibrinolytic system on material surfaces

“…Such a surface would mimic the naturally occurring fibrinolytic process that occurs on the surface of fibrin [8]. This concept has been pursued in our laboratories over the past several years [9][10][11][12][13][14][15][16][17][18][19][20][21]. The present contribution is intended, in part, as an elaboration of this concept and an outline of developments to date.…”

“…Therefore, it was appropriate to investigate the interactions of t-PA with our "plasminogen-exclusive" lysinized PU surfaces. Detailed studies of t-PA binding to these surfaces and the fate of adsorbed t-PA on exposure to plasma were undertaken [16]. The data obtained indicated that the -lysine surfaces had a high capacity for t-PA adsorption from buffer.…”