Fundamental measurements of liquid-liquid phase separation in lipid membranes and development of methods to assay domain compositions

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Each cell is surrounded by a membrane, and lipids in this membrane can demix into two coexisting liquid phases. This phenomenon is biologically important. For instance, when a yeast cell becomes nutrient limited, the membrane of its vacuole (an organelle) demixes. The current project is organized into five research themes on the production of artificial membranes and the study of their demixing transitions. The research will test if asymmetric lipid vesicles (which can mimic cell membranes) phase separate in the same way that entirely flat and taut membranes (which are less biologically relevant) phase separate. The project will have broader impacts of publishing new protocols and computer code, developing scientific teaching materials, and mentoring the next generation of scientifically-trained workers. Well-developed outreach activities include dissemination of scientific results, training of early-career scientists, and public outreach. Assessment plans for the Intellectual Merit and the Broader Impacts are presented.The research centers on the topic of liquid-liquid phase separation in membranes. Some of the problems the project addresses are technical. For example, the research seeks to develop a new, more accessible method of determining ratios of lipids in coexisting membrane phases and to analyze lipid compositions of vesicles made by a variety of methods. Other elements of the research are driven by theoretical predictions. For example, Raman imaging will be used to test predictions of the distributions of lipids across phases and their boundaries, and fluorescence microscopy will be used to test theories about asymmetry in the number and type of lipids in vesicle membranes. Other experiments will be exploratory. For example, one part of the project is to search for liquid-liquid phase separation in membranes with previously untested lipid compositions. Together, the different parts of the project present a balanced portfolio with goals of testing current theory, amassing quantitative data needed to evaluate simulations, developing methods that enable future quantitative measurements, and mentoring and training a future workforce that has strong scientific and technical skills.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.