With this award, the Chemistry of Life Processes is supporting Professor Elsa Yan and her co-PI, Professor Victor Batista, to develop an optical method to characterize protein structures at interfaces. Characterization of protein structures at interfaces is important for understanding biological functions of proteins associated with cell membranes. It is also important for developing biomaterials and biosensors to meet the needs in biotechnology. However, there has been a lack of real-time and in situ method that can provide selectivity of both interface and protein secondary structures. To bridge this technological gap, this proposal seeks to establish chiral sum frequency generation (SFG) spectroscopy into a robust method for unambigiuous identification of protein secondary structures in situ and in real time at interfaces.

The project is expected to have broader scientific impact as it may lead to related approaches to study other chiral macromolecules at interfaces, including native biopolymers (e.g., DNA and RNA) and synthetic polymers and supramolecular assemblies at interfaces. The method provides optical signatures of protein secondary structures free of optical background from aqueous solvent and achiral solutes. The proposed research applies quantitative physical methods to study biomolecular systems, which is incorporated into the education activities conducted by the principle investigator both in classrooms and laboratories. These activities target students at the levels of high school, undergraduate, graduate, and postdoctoral, providing them multidisciplinary training at the interface of biological and physical sciences.

Project Report

Proteins are large biological molecules that perform various functions in biological organisms. On cell membranes, proteins are involved in a variety of activities, such as the transportation of molecules, synthesis and decomposition of substances, and interactions between different cells. Because these activities are usually associated with the structural change of proteins on cell membranes, it is necessary to reveal the structures of proteins on surfaces. Conventional methods are not sufficient to fulfill the task because they are often unable to distinguish proteins inside and outside of cells from those on cell membrane surfaces, nor are they sensitive enough to unambiguously distinguish standard folds of protein structures. Funded by the National Science Foundation, we have developed chiral sum frequency generation spectroscopy (SFG) as a stand-alone technique to probe protein structures on cell membrane surfaces exclusively. We have achieved this by developing new experimental and theoretical tools. In terms of experiments, we have been characterized a series of proteins and established a series of chiral SFG signatures that can be used to distinguish various folded structures of proteins. In terms of theory, we have derived equations and formulas to describe the chiral SFG signatures quantitatively. With computational simulation, we have obtained a fundamental understanding about the origin of the chiral SFG signatures and extracted information about orientation of proteins on surfaces. These results have not only established chiral SFG as a unique tool to study proteins on cell membrane surfaces, but also provided a new methods to solve problems in biological and biomedical sciences, material sciences, colloidal sciences, electronics, and engineering.

National Science Foundation (NSF)
Division of Chemistry (CHE)
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David Rockcliffe
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Yale University
New Haven
United States
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