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: 0745786
• 负责人: Linda Hirst
• 金额: $ 57.28万
• 依托单位: Florida State University
• 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: 2008-02-01 至 2008-10-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0745786&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.

这项由佛罗里达州立大学材料研究部生物材料计划颁发的职业奖项，研究了胆固醇和多不饱和脂肪在脂质双层中的自组装及其对细胞膜的结构影响。这项提议是为了加深对细胞膜背后的基本物理学的理解，并无疑将在未来带来新的医学技术。此外，自组装的生物结构可以被定制成用于模板和形成纳米结构的各种应用。利用掠入射X射线衍射法(GIXD)和共振X射线衍射法(RXD)对膜系统进行了研究。利用体外脂类混合物，PI将研究生物活性分子对脂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，通过与其他脂类的相互作用，它可能通过影响膜的性质或通过诱导相分离进入脂类‘筏’，从而显著影响膜蛋白的功能；脂筏是细胞膜与周围区域组成不同的区域。在这个项目中，多不饱和脂肪酸将被结合到生物相关的脂双层及其与胆固醇的相互作用中。这种相互作用与视网膜视杆细胞外段的膜特性高度相关，在那里会出现高浓度的高度不饱和脂类，但它们的功能尚不清楚。为了进行这项工作，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，特别是平面有序性。荧光显微镜和原子力显微镜将补充这项工作，提供有关宏观膜结构和相分离的信息。尽管生物物理学很重要，细胞结构与活的有机体有关，但生命科学本科生在很大程度上仍然不了解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。这项提议旨在向生命科学专业的学生介绍厌恶物理的学生，了解生物分子相互作用的世界及其重要性。通过开发一门重要的新课程--生物医学物理学，国际医学联合会正致力于以新颖的、与生物相关的方式向本科生群体介绍物理科学主题。重点是吸引生命科学专业的女本科生体验物理研究，鼓励她们从事生物物理学事业。PI还将教授凝聚态物理的本科课程，其中包括生物分子组装和软物质方面的更高级主题，而不是传统的凝聚态主题。对这些课程的补充将是开发一个主要的新网站“softmatterworld.org”，重点是软物质物理，其中很大一部分将涉及生物物理和生物分子自组装。