CAREER: A Systematic Study of Cholesterol (Nano)Domains in Model Lipid Membranes

职业：脂质膜模型中胆固醇（纳米）域的系统研究

• 批准号: 0346638
• 负责人: Steven Wrenn
• 金额: --
• 依托单位: Drexel University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-01-15 至 2009-12-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0346638&HistoricalAwards=false
• 关键词: CAREER; Systematic; Study; Cholesterol; Nano

Wrenn, Steven P. - Drexel University"CAREER: A Systematic Study of Cholesterol (Nano) Domains in Model Lipid Membranes" This project is a systematic study of cholesterol domain formation that is undertaken to identify the regions in temperature-composition space in which structured domains form. The project would also identify the sensitivity of domain formation to physical parameters such as vesicle curvature and bilayer fluidity and to chemical parameters such as phospholipid chain length, degree of saturation, as well as the head group size and charge, and the kinetics and mechanisms of domain growth. The study of cholesterol domain formation in well controlled, model lipid membrane systems lays a foundation for understanding how cholesterol domains contribute to cholesterol nucleation from biological colloids. The research aims to provide a rigorous characterization of the recently discovered cholesterol domains. Specifically, this project consists of an exhaustive phase behavior study to identify regions in temperature-composition space in which cholesterol domains form. These complementary studies provide measurements of domain sizes using a combination of Forster resonance energy transfer and atomic force microscopy. Additional research assess whether domain size is sensitive to membrane curvature. Mathematical models and simulations are included to validate or refute experimental findings. Broader Impacts Cholesterol crystals in the body can be deadly. There are few fundamental studies describing how cholesterol crystallizes from colloidal particles such as vesicles or lipoproteins. The formation of cholesterol crystal may be the reason for a heart attack due to the sudden rupture of an atherosclerosic plaque. Cholesterol crystals may also explain the formation of gallstones. In both cases, the results from this research may prove to be useful in preventing cholesterol crystallization in the body.In terms of social and educational impact, a new mentorship program will target inner city students from Philadelphia, taking advantage of Drexel's close proximity, and will be called Philadelphia Inner City Education via Mentorship for the Under-Privileged (PIC-EM-UP). In particular, a dozen students will be selected from Philadelphia high schools and will be grouped into four teams of three students each. Each team will work alongside a faculty mentor on a mini-project relating to the faculty mentor's research area for one week. The research on cholesterol domains proposed herein will constitute one of the projects entitled "Cholesterol: The Good, the Bad, and the Nuclei." Each week, the teams will switch faculty mentors, working with a total of four mentors and four projects over a four-week period. A high school teacher will participate as a chaperone and will circulate among all teams to help students feel more comfortable in their new research environment.

Wrenn, Steven P. - 德雷塞尔大学“职业：脂质膜模型中胆固醇（纳米）结构域的系统研究” 该项目是对胆固醇结构域形成的系统研究，旨在识别温度组成空间中形成结构化结构域的区域。该项目还将确定域形成对囊泡曲率和双层流动性等物理参数的敏感性，以及对磷脂链长度、饱和度、头基大小和电荷等化学参数的敏感性，以及域生长的动力学和机制。在良好控制的模型脂质膜系统中对胆固醇结构域形成的研究为了解胆固醇结构域如何促进生物胶体中的胆固醇成核奠定了基础。该研究旨在对最近发现的胆固醇结构域提供严格的表征。具体来说，该项目包括一项详尽的相行为研究，以确定温度组成空间中形成胆固醇域的区域。这些补充研究结合福斯特共振能量转移和原子力显微镜提供了域尺寸的测量。其他研究评估了域大小是否对膜曲率敏感。数学模型和模拟被用来验证或反驳实验结果。更广泛的影响 体内的胆固醇晶体可能是致命的。很少有基础研究描述胆固醇如何从囊泡或脂蛋白等胶体颗粒中结晶。胆固醇晶体的形成可能是由于动脉粥样硬化斑块突然破裂而导致心脏病发作的原因。胆固醇晶体也可以解释胆结石的形成。 在这两种情况下，这项研究的结果可能被证明有助于预防体内胆固醇结晶。 在社会和教育影响方面，一项新的辅导计划将利用德雷克塞尔的地理位置，针对来自费城内城的学生，该计划将被称为“费城内城弱势群体辅导教育”(PIC-EM-UP)。具体来说，将从费城高中选出十几名学生，分为四组，每组三名学生。每个团队将与一名教师导师一起完成一个与该教师导师研究领域相关的小型项目，为期一周。本文提出的胆固醇领域研究将构成题为“胆固醇：好、坏和细胞核”的项目之一。每周，团队都会更换教师导师，在四个星期的时间内与总共四位导师和四个项目一起工作。一名高中老师将作为监护人参与，并在所有团队中进行巡视，以帮助学生在新的研究环境中感到更加舒适。