Blood coagulation reactions on nanoscale membrane surfaces

blood;coagulation;clotting;tissue factor;prothrombin;prothrombinase;thrombin;tenase;intrinsic;extrinsic;factor VIIa;nanotechnology;Nanodiscs;phospholipids;membranes;anionic;hemostasis;thrombosis;heart disease;hemostatic agent

Pureza, Vincent S.

关键词: blood;    coagulation;    clotting;    tissue factor;    prothrombin;    prothrombinase;    thrombin;    tenase;    intrinsic;    extrinsic;    factor VIIa;    nanotechnology;    Nanodiscs;    phospholipids;    membranes;    anionic;    hemostasis;    thrombosis;    heart disease;    hemostatic agent;   

Others  :  https://www.ideals.illinois.edu/bitstream/handle/2142/14739/Pureza_Vincent.pdf?sequence=2&isAllowed=y

美国|英语

来源: The Illinois Digital Environment for Access to Learning and Scholarship

【 摘 要 】

Blood coagulation requires the assembly of several membrane-bound protein complexes composed of regulatory and catalytic subunits.The biomembranes involved in these reactions not only provide a platform for these procoagulant proteins, but can also affect their function.Increased exposure of acidic phospholipids on the outer leaflet of the plasma membrane can dramatically modulate the catalytic efficiencies of such membrane-bound enzymes.Under physiologic conditions, however, these phospholipids spontaneously cluster into a patchwork of membrane microdomains upon which membrane binding proteins may preferentially assemble.As a result, the membrane composition surrounding these proteins is largely unknown.Through the development and use of a nanometer-scale bilayer system that provides rigorous control of the phospholipid membrane environment, I investigated the role of phosphatidylserine, an acidic phospholipid, in the direct vicinity (within nanometers) of two critical membrane-bound procoagulant protein complexes and their respective natural substrates.Here, I present how the assembly and function of the tissue factor·factor VIIa and factor Va·factor Xa complexes, the first and final cofactor·enzyme complexes of the blood clotting cascade, respectively, are mediated by changes in their immediate phospholipid environments.