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

Wrenn，Steven P. - Drexel University“CAREER：A Systematic Study of Cholesterol（Nano）Domains in Model Lipid Membranes”这个项目是一个胆固醇结构域形成的系统性研究，旨在确定温度组成空间中结构域形成的区域。该项目还将确定结构域形成对物理参数（如囊泡曲率和双层流动性）和化学参数（如磷脂链长度、饱和度以及头基大小和电荷）的敏感性，以及结构域生长的动力学和机制。在良好控制的模型脂质膜系统中胆固醇结构域形成的研究为理解胆固醇结构域如何有助于从生物胶体中胆固醇成核奠定了基础。该研究旨在为最近发现的胆固醇结构域提供严格的表征。具体而言，该项目包括一个详尽的相行为研究，以确定在胆固醇域形成的温度组成空间的区域。这些互补的研究提供了使用福斯特共振能量转移和原子力显微镜相结合的域大小的测量。其他研究评估域大小是否对膜曲率敏感。数学模型和模拟包括验证或反驳实验结果。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胶体颗粒如囊泡或脂蛋白中结晶。由于动脉粥样硬化斑块突然破裂，胆固醇结晶的形成可能是心脏病发作的原因。胆固醇结晶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会被证明是有用的，以防止胆固醇结晶在体内。在社会和教育的影响方面，一个新的导师计划将针对来自费城市中心的学生，利用德雷克塞尔大学的近距离优势，将被称为费城市中心教育通过导师为低收入者（PIC-EM-UP）。特别是，将从费城高中选出12名学生，并将他们分成四组，每组三名学生。每个小组将与一名教师导师一起进行一个与教师导师研究领域有关的小型项目，为期一周。本文提出的关于胆固醇结构域的研究将构成题为“胆固醇：好的，坏的，和核”的项目之一。“每周，这些团队将更换教师导师，在四周的时间内与总共四名导师和四个项目合作。一名高中教师将作为监护人参加，并将在所有团队中巡回，以帮助学生在新的研究环境中感到更舒适。

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.