Biophysical Measurements of Lipid Membranes to Investigate Miscibility, Critical Points, and Sterol Solubility

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Lipids in a membrane respond to particular changes in temperature or overall membrane composition by segregating into liquid domains with compositions that are distinct from the surrounding membrane. Furthermore, lipids in one leaflet of a bilayer membrane interact so strongly with lipids in the opposite leaflet that domains are induced from one side of a membrane to the other, even in the absence of membrane proteins. This project will probe the complex functions performed by lipid bilayers, with the eventual goal of shaping our knowledge of the physical behaviors accessible to cell membranes, and guiding biologists in new approaches to understanding complex biological systems. The primary tools of approaching these problems will be fluorescence microscopy and NMR. To investigate Inter-leaflet interactions and induction of domains across membrane leaflets, mechanisms of induction of liquid domains from one leaflet of a membrane to the other will be tested. To investigate local changes in lipid distributions versus global phase behavior, the effect of crosslinking of membrane components on membrane phase behavior will be evaluated. To study sterol solubility, NMR will be employed. To investigate whether liquid domains form in membranes containing lipids found in the inner leaflet of cell membranes (PE lipids, PS lipids, and PI lipids), vesicles containing those lipids will be produced and analyzed.The PI will directly advise undergraduate and graduate researchers and they will present their research results at national scientific meetings. The majority of graduate students in the Keller laboratory have been women. In the classroom, Dr. Keller will continue to improve the classroom resources she has developed such as a mathematics tutorial, an assignment that introduces students to research seminars and literature searches, and classroom content that emphasizes current research topics. Dr. Keller has recently been recognized for her accomplishments in the classroom with a UW Department of Chemistry Outstanding Teaching Award in 2005, and a University of Washington Distinguished Teaching Award in 2006. In the UW community, Dr. Keller will continue to participate in UW mentoring activities through presentations to the UW Faculty Connections students, the UW Undergraduate Research Society, the UW Chemistry Student Association, the UW Nanotech Student Association, and the UW Postdoctoral Association. In the surrounding community, Dr. Keller will continue to work to implement a centralized, searchable web listing of seminars on campus to enable local industry and community members to learn about relevant scientific research at the University of Washington. Dr. Keller will continue to disseminate materials that she has developed in order to mentor young faculty across the U.S.