Enhancing Protein Stability and Function by Confinement in Nanoporous Materials: Fundamental Understanding Using Experiments and Simulations

Rensselaer Polytechnic Institute, Troy NY

Investigators

Abstract

0967937 Coppens Structural changes of proteins adsorbed on the concave surface of nanoporous silica and othermaterials will be studied to understand how and why confinement affects their catalytic activity and thermal stability. Preliminary experimental investigations on high surface area, ordered nanoporous materials to be considerably extended in this project demonstrate the possibility to adsorb large quantities of several prototypical proteins at a high rate. Most significantly, a considerably increased enzymatic activity and stability was observed, apparently induced by strong interactions between the protein and a solid support whose pores are barely broader than the protein molecules. In order to understand such confinement of the investigators will carry out a systematic program of molecular simulations and calculations based on statistical mechanics, which focuses on systems of increasing complexity from homo and hetero polymers to proteins used in the experimental effort. This understanding is a prerequisite to designing a broad spectrum of applications from healthcare to catalysis, separations, sensing, and controlled release. Intellectual merit: Proteins frequently undergo structural changes when confined to nanopores, or tethered to a surface. These changes, which positively or negatively impact enzyme activity and stability, depend on the support protein pair and the properties of the medium, and remain poorly understood. Development and implementation of statistical mechanical theory aided by high performance computing helps us to gain fundamental understanding on how local curvature, as well as electrostatics, hydrophobicity and hydration influence protein structure, stability and activity in constrained environments. Detailed experimentation on well characterized, carefully synthesized nanoporous materials, with designed pore surface properties, completes the picture obtained by studies on protein adsorption on convex nanostructures, such as nanoparticles and nanotubes. This molecular insight can be incorporated into chemical engineering models of adsorption, diffusion and reaction. Progress on the synthesis of well structured nanomaterials allows validation of theoretical work, but it will also allow leveraging this knowledge to the synthesis of hybrid materials with rationally designed protein support interactions, and offer insights useful to biological systems. Broader impact: Fundamental insights gained by this study on protein confinement in nanoporous materials readily translate to the rational design and synthesis of hybrid nanomaterials that have transformative impact on technological applications varying from enzymatic catalysis and sensors to high throughput, selective (bio-) separations via chromatography and membranes for the production of therapeutics, and biomedical applications. The quantity of (expensive) protein could be reduced, its activity controlled, its stability increased, and recovery facilitated. In addition, this research program offers an enriching educational experience for graduate and undergraduate students. Concepts will be integrated in thermodynamics and reaction engineering classes. Women and underrepresented minorities will be specifically targeted for research participation. The New Visions METS program will be used to involve high school students and attract them to studies in science and engineering. Several female undergraduate students and a high school student were already involved in preliminary work. International exchanges will be strengthened, including collaboration with Dr. Ajayan Vinu at the National Institute of Materials Science (NIMS) in Tsukuba, Japan, in particular for experiments. The Japan Science and Technology Foundation already funded a semester of research at NIMS for one of the PI's graduate students on preliminary experiments in the area of this proposal. The ongoing Molecularium movie project, of which the co-PI is anexecutive producer, brings the world of atoms and molecules to life in an animation on the Big Screen, including a recent IMAX production, based on real molecular simulations