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

膜中的脂类对温度或整个膜组成的特殊变化作出反应，通过分离成具有与周围膜不同的组成的液体区域。此外，双层膜的一个小叶中的脂类与相反小叶中的脂类相互作用如此强烈，以至于即使在没有膜蛋白的情况下，结构域也会从膜的一侧诱导到另一侧。这个项目将探索脂质双层执行的复杂功能，最终目标是塑造我们对细胞膜可接近的物理行为的知识，并指导生物学家以新的方法理解复杂的生物系统。解决这些问题的主要工具将是荧光显微镜和核磁共振。为了研究小叶之间的相互作用和跨膜小叶诱导结构域，将测试从膜的一个小叶到另一个小叶诱导液体结构域的机制。为了研究脂类分布与整体相行为的局部变化，将评估膜组分的交联性对膜相行为的影响。为了研究甾醇的溶解度，将使用核磁共振。为了调查含有细胞膜内叶中的脂类(PE脂、PS脂和PI脂)的膜中是否形成液态域，将产生并分析含有这些脂类的囊泡。PI将直接为本科生和研究生提供建议，他们将在全国科学会议上展示他们的研究成果。凯勒实验室的大多数研究生都是女性。在课堂上，凯勒博士将继续改进她开发的课堂资源，如数学教程、向学生介绍研究研讨会和文献搜索的作业，以及强调当前研究主题的课堂内容。凯勒博士最近因其在课堂上的成就而受到表彰，她在2005年获得了华盛顿大学化学系杰出教学奖，并在2006年获得了华盛顿大学杰出教学奖。在威斯康星州大学社区，Keller博士将继续参与威斯康星州大学的辅导活动，向威斯康星州大学教师联谊会、威斯康星州本科生研究会、威斯康星州化学学生协会、威斯康星州纳米技术学生协会和威斯康星州博士后协会发表演讲。在周边社区，凯勒博士将继续致力于在校园内实施集中的、可搜索的研讨会网络清单，使当地行业和社区成员能够了解华盛顿大学的相关科学研究。凯勒博士将继续传播她开发的材料，以指导美国各地的年轻教师。

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.