This research program will address the grand challenge of identifying material properties that preserve or even enhance the stability of immobilized protein components in devices or materials. Many biological macromolecules have unique, useful properties that are exploited in applications ranging from biosensors to drug carriers that seek out diseased cells in the body. But these applications typically require incorporating proteins into non biological materials in ways that completely alter the protein environment and often destroy the very properties sought. In this research, the PIs will address the grand challenge of determining how to engineer material properties to preserve (or shut down) these unique protein functions. Results from this research will have broad impact, by uncovering guidelines for how to engineer material microenvironments that are fit for proteins. Because of the widespread use of immobilized bio-macromolecules in industry and in research, the PIs findings will have broad impact across a range of disciplines. Through several outreach activities, the PIs will also expose middle school girls and minority students to this exciting research and the many ways our discoveries can have a positive impact on society.
Technical To address the challenge of preserving immobilized protein stability, this program will use two powerful, complimentary experimental approaches. First, molecular force measurements will identify the nanoscale surface properties associated with surface chemistries that determine how materials interact with proteins. Next, the PIs will establish how those nanoscale properties alter protein stability, by using novel temperature-jump measurements to measure the folding rates of immobilized proteins. The use of nanoscale force measurements and temperature-jump measurements at submicron resolution will uniquely identify causal relationships between molecular scale interfacial force fields and the surface chemistries that protect or shut down protein function. This program extends prior investigations of thermally responsive poly(N-isopropylacrylamide) to zwitterionic coatings, which display exceptional protein-resistant properties and apparent protein/bio-compatibility, despite significant differences in composition and architecture. Molecular force measurements and transformative surface-specific temperature-jump measurements will reveal physical chemical coupling between the surface microenvironment and protein folding stability. These studies will bridge the gap between nanoscale surface chemistries and immobilized protein folding stability, and identify transformative new design rules for engineering protein-protective microenvironments.
