CAREER: Self-Assembly of Polyunsaturated Lipids and Cholesterol In The Cell Membrane

职业：细胞膜中多不饱和脂质和胆固醇的自组装

• 批准号: 0852791
• 负责人: Linda Hirst
• 金额: $ 52.91万
• 依托单位: University of California - Merced
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-07-01 至 2013-01-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0852791&HistoricalAwards=false
• 关键词: CAREER; Self; Assembly; Polyunsaturated; Lipids

This Career award by the Biomaterials program in the Division of Materials Research to Florida State University investigates the self-assembly of cholesterol and polyunsaturated lipids in the lipid bilayer and their structural effects on the cell membrane. This proposal is to develop understanding of the fundamental physics behind the cell membrane, and will undoubtedly lead to new medical technologies in the future. In addition, self-assembled biological structures can be tailored to a variety of applications for templating and the formation of nanostructures. This proposal focuses on the study of membrane systems using grazing incidence x-ray diffraction (GIXD) and resonant x-ray diffraction. Using in-vitro lipid mixtures, the PI will investigate the effects of biologically active molecules on the structure and physical properties of the lipid bilayer. Cholesterol is one of the most important components of the cell membrane, and through interactions with other lipids, it may influence membrane protein function significantly by affecting membrane properties or by inducing phase separation into lipid 'rafts'; areas of the cell membrane with a differing composition to the surrounding regions. In this project, polyunsaturated fatty acids will be incorporated into biologically relevant lipid bilayers and their interactions with cholesterol. This interplay is highly relevant to membrane properties in the retinal rod cell outer segment, where high concentrations of highly unsaturated lipids occur, but their functions are not well understood. To carry out this work, the investigators will use synchrotron x-ray techniques to study bilayer structure in different lipid mixtures, particularly in plane ordering. Fluorescence microscopy and atomic force microscopy will complement this work, giving information on macroscopic membrane structure and phase separation. Despite the importance of biological physics and the relevance of cellular structure to the living organism, undergraduate life-science students remain largely unaware of the physics of bio-molecules and their interactions on the nano-scale, where fundamental forces control the assembly of all supra-molecular structures found in the cell. This proposal aims to introduce students in life-science majors with an aversion to physics, to the world of bio-molecular interactions and their importance. By developing a major new course, "Biomedical Physics", the PI is working to introduce physical science topics to the undergraduate student population in novel, biologically related ways. A key focus is to attract female undergraduate students in life science majors to experience research in physics and to encourage them to pursue a career in biophysics. The PI will also teach an undergraduate course in condensed matter physics that includes more advanced topics in biomolecular assembly and soft matter to the traditional condensed matter topics. These courses will be complemented by the development of a major new web-site "softmatterworld.org" focusing on soft-matter physics, a significant proportion of which will involve biophysics and bio-molecular self-assembly.

该职业奖由佛罗里达州立大学材料研究部的生物材料项目授予，研究胆固醇和多不饱和脂质在脂质双层中的自组装及其对细胞膜的结构影响。这一提议旨在加深对细胞膜背后的基本物理学的理解，无疑将在未来引领新的医疗技术。此外，自组装的生物结构可以被定制为用于模板化和纳米结构的形成的各种应用。该提案的重点是研究膜系统使用掠入射X射线衍射（GIXD）和共振X射线衍射。使用体外脂质混合物，PI将研究生物活性分子对脂质双层结构和物理性质的影响。胆固醇是细胞膜最重要的成分之一，通过与其他脂质的相互作用，胆固醇可能会通过影响膜特性或通过诱导相分离成脂质“筏”而显著影响膜蛋白功能;细胞膜的区域与周围区域具有不同的组成。 在这个项目中，多不饱和脂肪酸将被纳入生物相关的脂质双层及其与胆固醇的相互作用。这种相互作用与视网膜视杆细胞外段的膜特性高度相关，其中存在高浓度的高度不饱和脂质，但它们的功能还不清楚。为了开展这项工作，研究人员将使用同步加速器X射线技术来研究不同脂质混合物中的双层结构，特别是平面有序。 荧光显微镜和原子力显微镜将补充这项工作，提供宏观膜结构和相分离的信息。尽管生物物理学的重要性和细胞结构与生物体的相关性，本科生命科学专业的学生仍然在很大程度上不知道生物分子的物理学及其在纳米尺度上的相互作用，在纳米尺度上，基本力控制着细胞中发现的所有超分子结构的组装。该提案旨在向生命科学专业的学生介绍厌恶物理学的生物分子相互作用及其重要性。通过开发一个主要的新课程，“生物医学物理”，PI正在努力介绍物理科学的主题，以新颖的，生物相关的方式向本科生群体。 一个关键的重点是吸引生命科学专业的女本科生体验物理学研究，并鼓励她们从事生物物理学职业。PI还将教授凝聚态物理学的本科课程，其中包括生物分子组装和软物质的更先进的主题，以传统的凝聚态主题。这些课程将通过开发一个主要的新网站“softmatterworld.org”来补充，该网站专注于软物质物理学，其中很大一部分将涉及生物物理学和生物分子自组装。