Responsive Tethered Polymer Layers: Protein Adsorption, Phase Transition and Interactions

Purdue University, West Lafayette IN

Investigators

Abstract

Igal G. Szleifer Purdue University "Responsive Tethered Polymer Layers: Protein Adsorption, Phase Transition and Interactions" The aim of this research is the theoretical study of the behavior of tethered polymer layers that can reversibly or irreversibly switch their properties upon change in an experimentally controlled variable, such as temperature, pH or salt concentration. The understanding of the behavior of these layers is a fundamental step towards the molecular design of non-fouling surfaces, biocompatible materials, drug delivery systems and sensors among many others. The work will concentrate on the structural and thermodynamic changes in the polymer layers and how these changes affect: (i) The ability of the layer to adsorb or reject protein (or nanoparticle) adsorption and (ii) The interactions of the polymer layer with other surfaces. The theoretical studies will be based on a molecular theory, developed by the PI, that has been successfully applied to study the thermodynamics and kinetic of protein adsorption, as well as the structural and thermodynamic properties of tethered polymer layers. Further, atomistic molecular dynamics simulations will be used to study pH sensitive peptides. The research will be carried out in close collaboration with two experimental groups. The specific polymeric systems to be studied include: 1) thermo-responsive polymer layers, 2) poly-ethylene oxide (PEO) functionalized with charged moieties and with bioactive ligands and 3) block copolymers of PEO with pH sensitive peptides. The first two systems are aimed at controlling protein adsorption and the ability to reversibly switch from adsorbing to non-adsorbing surfaces. The pH sensitive peptides are aimed at controlling the adhesion of the polymer modified layers with lipid bilayers or other hydrophobic surfaces/interfaces. Intellectual merit of the proposed activity This research activity is at the intersection of engineering, physics, chemistry and biology. It combines: 1) The fundamental understanding of complex systems where the relevant length scale is nanometers with time scales that range from milliseconds to hours, with 2) The practical application in the design of biomaterials, drug carriers and nanosensors among others. Thus, this research would combine atomistic computer simulations to understand detailed interactions and solvation with molecular theory that uses more coarse-grained models than the simulations. Furthermore, the molecular approach enables the systematic study of the kinetics, structural and thermodynamic properties of large systems. The ongoing collaborations with the experimental groups of Profs. Thompson (Purdue) and Genzer (NCSA), with its already proven track record, provides the necessary framework to maintain the theoretical work in a practical and applied environment at all stages. Broader impact from the proposed activity The research program will involve the participation of graduate and undergraduate students. In particular, the PI plans to attract undergraduate research students from underrepresented minorities by participating in the successful MARC/AIM program and by linking the research projects with the "Summer Institute for Diversity in Biomedical Science", both administered by the Minority Program of the Graduate School at Purdue University. The research work will be further integrated into undergraduate education, and at a later stage even high school education, by collaboration with Prof. Weaver (Chemical Education, Purdue). This integration will result in the development of multimedia and interactive DVD's that incorporate research data to apply the concepts learned in the classroom. The research findings will be available in a popular version in the web page of the PI. There will be tutorials for the application of the molecular theory and computer simulations for the non-experts, as well as a simple description of the research outcomes and their relevance to many fields in engineering and science.