Biophysics of protein interactions on membrane surfaces

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Many critical cellular functions are regulated by protein interactions in the plasma membrane. Quantitative measurements of protein interactions in membranes, however, are challenging to perform due to many limitations of current experimental methodologies. This work will advance quantitative biophysical tools and will provide the broad scientific community with better methods to study membrane protein folding, structure, and function. Ultimately, improvement in methods will lead to discoveries that help reveal the role of interactions on membrane surfaces and their biological function in cells. The project will support training and the professional development of graduate and undergraduate students at Johns Hopkins University. This project will also provide educational and training opportunities for young scientists from diverse backgrounds and for students from Baltimore City Schools. The goal of the research is to develop a general biophysical methodology that can uncover the strength and the mechanism of interactions that occur on the membrane surface, between membrane receptors and cytoplasmic proteins. These interactions have profound biological significance, as they trigger the propagation of biochemical signals from the plasma membrane to the cytoplasm. They are very common in biology, as membrane receptors are known to interact with multiple cytoplasmic partners. Yet, these processes are complex and poorly understood. The strength of the interactions between membrane receptors and cytoplasmic proteins can depend on the association state of the receptor. The soluble partners, in turn, can modulate the interactions of the receptors in the membrane. Quantitative details, as well as biophysical methods that can yield such quantitative details, are lacking. The protocols that will be developed in this project will fill a large gap in methodology. They can be used for any combination of a membrane protein and soluble protein, and can reveal many new interactions. This project is jointly supported by the Molecular Biophysics Cluster of the Molecular and Cellular Biosciences Division in the Directorate for Biological Sciences and by the Biomaterials Program of the Division of Materials Research in the Directorate for Physical and Mathematical Sciences.