Blood coagulation reactions on nanoscale membrane surfaces

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.

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Biochemistry

Grantor

University of Illinois at Urbana-Champaign

Year dc:date

2010

Author dc:creator

• Pureza, Vincent S.

Contributors dc:contributor

• Morrissey, James H.
• Schwartz, Bradford S.
• Sligar, Stephen G.
• Tajkhorshid, Emad

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

Statement dc:rights

• Copyright 2009 Vincent S. Pureza

Language dc:language

en

Handle dc:identifier

http://hdl.handle.net/2142/14739

OAI identifier oai:identifier

oai:www.ideals.illinois.edu:2142/14739