Leveraging 2D and 3D interactions to understand structural transitions in model and cell membranes from molecular to micron scales

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All cells are surrounded by a cell membrane, and this project will directly measure the distributions of molecules within models of cell membranes. The results of this research will be important and of benefit to society because the distribution can determine how a protein in the membrane functions and whether a cell lives or dies. Additional societal benefit is that the project will generate new designs for microfluidic devices and new protocols for visualizing membranes on nanometer scales by cryo-electron microscopy. The designs and protocols will be made widely available in scientific publications. This project will also prepare student researchers for challenging careers in science and engineering. Graduate and undergraduate researchers will produce samples, test hypotheses, analyze their data, present their results at conferences, and publish their results. The project includes additional activities designed to inspire, train, and mentor the next generation of scientists and citizens through outreach projects. Many types of biophysical membranes spontaneously demix into micron-scale liquid domains enriched in specific lipid (and protein) types. The systems range in complexity from "simple" model membranes composed of only a few lipid types, to complex membranes derived from cells, or organelle membranes in yeast. The research will answer the following biologically-motivated questions: How do changes in membrane physical parameters affect the size, shape, and transition temperatures of liquid domains in membranes? How do interactions of membranes with bulk solutions affect membrane shapes and miscibility transitions? How does membrane demixing affect peptide structure and partitioning? Beyond answering these questions, the goals of the project are to translate the resulting discoveries to the biology community by showing how physical phenomena suggest new approaches for understanding complex biomembrane systems. The tools that will be employed include fluorescence microscopy, microfluidics, and cryo-electron microscopy. The project will be a vehicle for training graduate and undergraduate students for challenging careers in science and engineering.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.