Transforming fundamental biological questions about cell membranes into quantitative experiments using model and cell systems

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Mammals, including humans, are built out of cells. Mammalian cells are bounded by an outer membrane composed of lipids, cholesterol, and proteins. These three types of molecules are distributed nonuniformly across the cell's outer membrane, and this heterogeneity is reported to influence disease processes. However, scientists currently have little understanding of how this heterogeneity arises in cell membranes. This issue and a host of other fundamental questions about cell membranes are impractical to address in intact cells. As a result, this project will utilize simpler, tractable membrane systems. In the first case, membranes will be composed of only lipids and cholesterol. In the second case, membranes will be derived from mammalian cell outer membranes. In both cases, the membranes will be nonuniform. In this project, the researchers will conduct a series of experiments to understand the conditions underwhich heterogeneity arises within lipid membranes. The long-­term goal of the project is to discover fundamental physical phenomena of lipid membranes that will subsequently prove applicable and relevant to biological cell membranes and to biotechnological applications. The researchers will convey the excitement and relevance of their results nationwide through press releases, public lectures, K-­12 outreach, and scientific journal articles. The principal investigator will train graduate students and undergraduates for careers in STEM fields and will mentor STEM faculty.The behavior of membranes, even of relatively simple model membranes, is remarkably rich.This project will investigate membranes that segregate into domains enriched in specific lipid (and protein) types in both model lipid bilayers and in membranes derived from cell systems. The objective of the research is to understand what physical mechanisms render domains stable, what physical parameters distinguish domains from other membrane regions, and which structural features of lipids are required for domain formation. The research is question-­driven rather than technique-­driven; an array of tools will be deployed including imaging of membranes on solid supports by atomic force microscopy and imaging of free-­floating vesicles by fluorescence microscopy.