Understanding Highly Heterogeneous Biological Membranes

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Biological membranes are more than barriers between cell compartments. These highly complex environments play a central role in a wide range of functions, including energy production, sensing, and communication. Structure on every length scale is a hallmark of biology, and cell membranes are no exception. Membranes contain hundreds of unique lipids organized on a nanometer length scale, and this organization is critical for cellular function. Abnormal lipid distributions have been linked to cell diseases. This project will investigate the local geometries, environments, and dynamics that dictate the membrane architecture and how membrane architecture relates to biological function. The PI is actively involved in undergraduate and high school student researcher programs: NSF REU, Moncrief Summer Internship, and Welch Summer Scholars Programs and will embark on a recruiting campaign to increase the number of underrepresented students enrolled in the graduate program at UT-Austin. This project will provide an excellent platform for training visiting students who join PI's research group. This will involve visits to Hispanic-serving Institutions in Texas and across the Southwest to advertise the program, network with faculty, and advise students on assembling competitive graduate school applications.In this project, the research team will investigate multiple aspects of heterogeneous membranes using a combination of vibrational spectroscopy and enhanced-sampling molecular dynamics simulations. The following aspects of membranes will be the primary focus of the project: 1. The team will characterize how individual lipid species sample a different range of local environments in a mixture with other lipids, as opposed to single-component, uniform bilayers, which are commonly used as biophysical models. For these reasons, this project seeks to establish a molecular-level view of lipid interactions to inform the importance of membrane diversity, and what specific interactions are not captured by the models. 2. The team will determine how membranes are perturbed by biologically-relevant ions such as Ca2+, and Mg2+. Negatively-charged lipids are known to interact strongly with these ions. Cells have multiple mechanisms to tightly control ion concentrations. These ions are predicted to disrupt the balance of local interactions among lipids and alter membrane properties. 3. This project will examine the role of protein crowding in perturbing lipid-lipid interactions. Biological membranes are packed with proteins. Up to 20% of the membrane area is occupied by proteins, which implies that lipids not only interact with other lipids but also with protein sidechains. The team will investigate how lipid-lipid interactions are modified by the presence of proteins.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.