Preparation and Properties of Lipid Vesicles With Highly Controlled Lipid Asymmetry

高度控制脂质不对称性的脂质囊泡的制备和性质

• 批准号: 1404985
• 负责人: Erwin London
• 金额: $ 39万
• 依托单位: SUNY at Stony Brook
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-01 至 2017-09-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1404985&HistoricalAwards=false
• 关键词: Preparation; Properties; Lipid; Vesicles; Highly

Nontechnical: This award by the Biomaterials Program in the Division of Materials Research to State University of New York at Stony Brook is to study membranes of living cells composed of lipids (specialized fat molecules) and proteins. Membranes control the uptake of food stuffs into cells and the communication between cells and their environment. Cell membranes are very complex, consisting of thousands of types of different proteins and lipids. Artificial membrane vesicles, composed of membrane lipids and proteins which are forming an envelope similar to a cell membrane, are important tools in understanding how membranes function. Natural membranes have two layers of membrane lipids, and they are asymmetric with different types of lipids in each layer. A key limitation in the utility of artificial membranes has been their lack of lipid asymmetry. Investigators of this award earlier discovered a method to prepare asymmetric artificial membranes. The proposed research on artificial membranes is expected to greatly expand the scientific knowledge on membranes. Additionally, this project will also have a broad impact on career development of future scientists, including minority students, by training both graduate and undergraduate students (including via contacts with other local institutions) in the conduct of research, experimental principles, and experimental techniques used in membrane research. Students will also be trained in proper conduct of scientific studies, scientific writing and speaking, which will prepare them for careers in research, teaching, or allied fields.Technical: Lipid asymmetry, a difference in the lipid composition in the inner and outer leaflets (monolayers) of a biological membrane, is a crucial property of the lipid bilayer in many cell membranes. Artificial vesicles (liposomes) containing lipid bilayers are biomaterials that have proven invaluable models of biological membranes, but the lack of methods to prepare asymmetric vesicles has limited their utility. With this grant, the first goal will be to prepare vesicles with inside-out asymmetry (cytosolic lipids facing outwards); to prepare vesicles containing a wide variety of outer leaflet lipids; and to prepare artificial asymmetric fungal membranes and bacterial outer membranes. The second goal will be to incorporate membrane proteins into asymmetric vesicles. The third goal will be to use asymmetric vesicles to tackle the biologically important issue of coupling between inner and outer leaflet physical properties. Such coupling has been proposed to contribute to signal transduction across biomembranes. To better understand the coupling between the outer and inner layers and signal transactions between them, fluorescent and neutron scattering studies will be carried out in collaboration with scientists at Oak Ridge National Laboratory. Additionally, this project will have a broad educational impact on career development of future scientists, including minority students, by training both graduate and undergraduate students (including via contacts with other local institutions). Students will receive specialized training in a variety of biochemical and spectroscopic techniques used in this study of membrane proteins and lipids, including unique methods developed in this investigator's laboratory. Students will also be trained in proper conduct of scientific studies, and writing and speaking skills, preparing them for careers in field of biological/biophysical sciences and/or teaching. Finally, by developing improved model for membrane systems, this project should broadly impact the field of membrane biology, including drug delivery and nanomaterial applications.

非技术性：该奖项由材料研究部生物材料计划授予斯托尼布鲁克的纽约州立大学，旨在研究由脂质（专门的脂肪分子）和蛋白质组成的活细胞膜。膜控制着细胞对食物的摄取以及细胞与环境之间的通讯。细胞膜非常复杂，由数千种不同的蛋白质和脂质组成。人工膜囊泡由膜脂和蛋白质组成，形成类似于细胞膜的包膜，是了解膜功能的重要工具。天然膜具有两层膜脂质，并且它们是不对称的，每层中具有不同类型的脂质。人工膜应用的一个关键限制是它们缺乏脂质不对称性。该奖项的研究人员早些时候发现了一种制备不对称人工膜的方法。对人工膜的拟议研究预计将大大扩展有关膜的科学知识。此外，该项目还将对未来科学家的职业发展产生广泛影响，包括少数民族学生，通过培训研究生和本科生（包括通过与其他当地机构的联系）进行研究，实验原理和膜研究中使用的实验技术。 学生还将接受科学研究，科学写作和演讲的适当行为的培训，这将为他们在研究，教学或相关领域的职业生涯做好准备。技术：脂质不对称性，生物膜内外小叶（单层）脂质组成的差异，是许多细胞膜中脂质双层的重要性质。含有脂质双层的人工囊泡（脂质体）是已被证明是生物膜的宝贵模型的生物材料，但缺乏制备不对称囊泡的方法限制了它们的实用性。有了这笔资金，第一个目标将是制备具有内向外不对称性（胞质脂质朝外）的囊泡;制备含有各种外部小叶脂质的囊泡;以及制备人工不对称真菌膜和细菌外膜。第二个目标是将膜蛋白整合到不对称囊泡中。 第三个目标将是使用不对称囊泡来解决内外小叶物理性质之间耦合的生物学重要问题。 已经提出这种偶联有助于跨生物膜的信号转导。为了更好地了解外层和内层之间的耦合以及它们之间的信号交易，将与橡树岭国家实验室的科学家合作进行荧光和中子散射研究。此外，该项目将通过培训研究生和本科生（包括通过与其他地方机构的联系），对未来科学家的职业发展产生广泛的教育影响，包括少数民族学生。学生将接受各种生物化学和光谱技术的专门培训，这些技术用于膜蛋白和脂质的研究，包括本研究员实验室开发的独特方法。学生还将接受科学研究，写作和口语技能的适当进行培训，为他们在生物/生物物理科学和/或教学领域的职业生涯做好准备。最后，通过开发膜系统的改进模型，该项目将广泛影响膜生物学领域，包括药物输送和纳米材料应用。