ID: MPS/DMR/BMAT(7623) 0804873 PI: Siedlecki, Christopher ORG: Penn State Medical College
Title: Protein Adsorption and Activity on Phase Separated Polymers
INTELLECTUAL MERIT: Polyurethane biomaterials dominate blood-contacting applications, but the fundamental basis for the hemocompatibility of these materials has yet to be understood. The goal of this proposal is to elucidate fundamental relationships between polyurethane microphase separated structures having characteristic dimensions similar to plasma proteins and biologic responses at the molecular scale by judicious application of materials imaging, characterization, and molecular analysis. In particular, the proposal seeks to relate polyurethane phase segregation at the hydrated polymer interface with the activity of adsorbed proteins to test the central hypothesis that: The chemical nature and nanoscale properties of phase separated biomaterials creates a distribution of unique interfacial environments that, in aggregate, influences conformation and activity of adsorbed blood-plasma proteins, in a manner that understandably correlates with phase distribution and chemistry. This hypothesis will be tested by investigating the role that molecular level surface properties play on the adsorption, structure and activity of plasma proteins in surface-induced thrombogenesis through completion of the following three tasks. (1) Characterize the interfacial environment of the separated microphases under physiologic buffer conditions for films of polyurethane copolymers by using atomic force microscope probes modified with self-assembled monolayers of controlled chemistry and with relevant plasma proteins. Determine the distribution of microdomains and the surface area occupied by both individual domains and hard segment/soft segment in aggregate for different polymer chemistries. (2) Quantify the adsorption of selected proteins to hard and soft polyurethane domains using atomic force microscopy under physiologic buffer conditions. (3) Determine changes in individual protein molecules by assessing the activity of adsorbed proteins using functional labeling of individual protein molecules and AFM bioadhesion measurements in order to establish structure/function relationships for each of the different polymer phases. Compare molecular measurements to traditional platelet adhesion measurements in order to address the role of microdomain properties on hemocompatibility.
BROADER IMPACTS: A persistent issue for materials intended for applications in contact with living tissue is compatibility between the tissue and the exogenous material. Materials intended for contact with blood must not provoke clotting if they are to be useful. This study addresses fundamental issues of blood protein-biomaterial interactions. While focusing on polyurethane materials, the generality of its approach promises to illuminate the broader field of protein-biomaterial compatibility. Integration of research and education is addressed here primarily in terms of research experience for students. Postdoctoral and summertime undergraduate students will be supported by the award. The PI has an excellent record of hosting high school students in his laboratory and plans to continue this practice.
|Effective start/end date
|9/1/08 → 8/31/12
- National Science Foundation: $375,000.00