Interaction of polystyrene/ poly(γ-benzyl l-glutamate) and poly(methyl methacrylate)/ poly(γ-benzyl l-glutamate) block copolymers with plasma proteins and platelets

Abstract

A-B-type block copolymers, consisting of polystyrene (PST) or poly(methyl methacrylate) (PMMA) forming segment (A) and poly(γ-benzyl l-glutamate) {P[Glu(OBzl)]} segment (B), were synthesized and the thrombus formation on these block copolymer films was investigated in relation to the adsorption of8 plasma proteins and the activation of platelets. The relative amount of thrombus formation was higher on homopolymers than on block copolymers. The amount of thrombus formation became less, with decreasing content of P[Glu(OBzl)] in the PST block copolymers and with increasing content of P[Glu(OBzl)] in the PMMA block copolymers. Adsorption of bovine serum albumin(BSA), bovine γ-globulin (BγG) and bovine plasma fibrinogen(BPF) onto polymer films was also investigated. More proteins were adsorbed and denatured when adsorped onto PST and PMMA than onto block copolymers. With increasing content of P[Glu(OBzl)] in the PST block copolymers, the degree of denaturation of adsorbed proteins increased, while the amount of protein adsorption was unaffected. Conversely, with increasing content of P[Glu(OBzl)] in the PMMA block copolymers, the degree of denaturation of adsorbed proteins decreased, while similarly the amount of protein adsorption was unaffected. Adhesion of platelets from platelet suspension (WP) to polymer films coated with one of the plasma proteins showed that the activation of adhered platelets was suppressed when there was a lower degree of denaturation of coated proteins. In the same experiments using platelet-rich plasma(PRP), neither the number of platelets adhered nor the degree of activation of the adhered platelets was correlated with the composition of the polymer films. These experimental results indicated that vinyl polymer/polypeptide block copolymers with certain compositions suppress the denaturation of adsorbed proteins and the activation of adhered platelets, thus leading to a slower rate of thrombus formation. However, the experiments using PRP suggest the intervention of minor plasma proteins other than the three major plasma proteins, and blood clotting factors other than platelets in thrombus formation.