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.

生物材料计划在佛罗里达州立大学的材料研究部颁发的职业奖调查了脂质双层中胆固醇和多不饱和脂质的自组装及其对细胞膜的结构影响。该建议是为了发展对细胞膜背后的基本物理学的理解，并无疑将导致未来的新医疗技术。此外，可以根据各种应用和形成纳米结构来量身定制自组装的生物结构。该建议着重于使用放牧发动机X射线衍射（GIXD）和谐振X射线衍射的膜系统的研究。使用体外脂质混合物，PI将研究生物活性分子对脂质双层的结构和物理特性的影响。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，它可能通过影响膜特性或诱导相位分离成脂质“筏”来显着影响膜蛋白功能。细胞膜的区域与周围区域不同。 在这个项目中，多不饱和脂肪酸将掺入生物学相关的脂质双层及其与胆固醇的相互作用中。该相互作用与视网膜杆细胞外部段中的膜特性高度相关，那里发生高浓度的高度不饱和脂质，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，尤其是在平面顺序中。 荧光显微镜和原子力显微镜将补充这项工作，从而提供有关宏观膜结构和相位分离的信息。尽管生物物理学的重要性以及细胞结构与生物体的相关性，但本科生的生活科学学生在很大程度上仍然没有意识到生物分子的物理学及其在纳米尺度上的相互作用，基本力量控制了在细胞中发现的所有上跨分子结构的组装。该建议旨在以对物理学的厌恶，生物分子互动的世界及其重要性介绍生命科学专业的学生。通过开发一个主要的新课程“生物医学物理学”，PI正在努力将物理科学主题引入新颖的学生与生物学相关的方式。 一个重点是吸引女性科学专业的女性本科生来体验物理学研究，并鼓励她们从事生物物理学的职业。 PI还将在传统的凝结物质主题中教授凝结物理学的本科课程，其中包括生物分子组装中更先进的主题和软物质。这些课程将与重点介绍软体物理的主要新网站“ SoftMatterWorld.org”的开发相辅相成，其中很大一部分将涉及生物物理学和生物分子自组件。