Protein Interactions with Nano-Scale Controlled Surfaces: The Molecular Basis for Non-fouling Behavior

University Of Washington, Seattle WA

Investigators

Abstract

ABSTRACT - 0433753 Surface resistance to protein adsorption is currently a subject of great interest and is critical to the performance of biosensors, implanted biomaterials, and drug carriers. Since proteins have distinct shapes and surface functionalities, protein adsorption is strongly dependent on the nano-scale chemical and structural properties of the surface. Despite extensive research in protein adsorption, there is still a lack of a molecular-level understanding of the non-fouling mechanism. Combined experimental and simulation studies proposed in this work will target this important problem. Intellectual Merit: From recent simulation and experimental studies from the PI.s group supported through a NSF SGER grant (1/1/03-3/31/04), it appears that there is a correlation between the non-fouling properties of oligo (ethylene glycol) (OEG) self-assembled monolayers (SAMs) and the hydration/flexibility of OEG chains. However, there is a lack of experimental measurements of the content and structure of water molecules bound in OEG chains. There has been no direct evaluation of the interaction forces between a protein and an OEG surface from molecular simulations in order to elucidate the molecular origin of surface resistance to protein adsorption. Furthermore, there are unresolved issues about when OEG- or poly(ethylene glycol) (PEG)-based materials work or fail, particularly at higher temperatures. In order to provide a complete and solid understanding of the non-fouling mechanism at the molecular level, three important problems will be tackled in this work: (a) to obtain force-versus-distance curves as a protein molecule approaches an OEG SAM surface from molecular simulations, (b) to probe the amount and structure of water molecules bound in OEG chains using combined quartz crystal microbalance (QCM)/surface plasmon resonance (SPR) experiments, and (c) to study the non-fouling mechanism of OEG SAMs at higher temperatures using SPR. Since the molecular details of a surface are of great importance to protein adsorption, OEG surface density and structure will be altered using either mixed OEG/OH SAMs or mixed ethanol and water assembly solvents. Hydrophobic CH3 and hydrophilic OH terminated SAMs will be used throughout these studies as reference systems. All the SAMs used in these studies will be fully characterized using X-ray photoelectron spectroscopy (XPS) and atomic force microscopy (AFM). Broader Impact: The success of this one year project will advance our fundamental understanding of the non-fouling mechanism at the molecular level, provide new criteria to evaluate non-fouling materials, and assist the design of new non-fouling materials. It will have significant impact on various applications ranging from biosensors to biomaterials, drug delivery, and tissue engineering to marine coatings. While non-fouling surfaces are critical to these technologies, a fundamental study of the non-fouling mechanism is a driving force for discoveries of new anti-fouling materials and coatings. Graduate and undergraduate students will be involved in this project, particularly students from underrepresented groups. Undergraduate researchers will be recruited through well-established outreach programs at local research centers, in which the PI has been actively involved. The knowledge will be disseminated through the courses, such as. Frontiers in Nanotechnology., .Computational Simulation and Modeling of Materials.