Understanding Highly Heterogeneous Biological Membranes

生物膜不仅仅是细胞间的屏障。这些高度复杂的环境在能源生产、传感和通信等广泛功能中发挥着核心作用。每一个长度尺度上的结构都是生物学的标志，细胞膜也不例外。膜含有数百种独特的脂质，这些脂质以纳米长度尺度组织，这种组织对细胞功能至关重要。脂质分布异常与细胞疾病有关。这个项目将调查当地的几何形状，环境和动力学，决定膜结构和膜结构如何与生物功能。PI积极参与本科和高中学生研究计划：NSF REU，Moncrief暑期实习和Welch暑期学者计划，并将开展招聘活动，以增加在UT-奥斯汀研究生课程就读的代表性不足的学生人数。这个项目将为参加PI研究小组的访问学生提供一个很好的培训平台。 这将涉及到在得克萨斯州和整个西南部的西班牙裔服务机构的访问，宣传该计划，网络与教师，并建议学生组装有竞争力的研究生院应用程序。在这个项目中，研究小组将调查多个方面的异质膜使用振动光谱和增强采样分子动力学模拟相结合。膜的以下方面将是该项目的主要重点：1.该团队将描述单个脂质物种如何在与其他脂质的混合物中对不同范围的局部环境进行采样，而不是通常用作生物物理模型的单组分均匀双层。出于这些原因，该项目旨在建立脂质相互作用的分子水平视图，以告知膜多样性的重要性，以及模型未捕获的特定相互作用。2.该团队将确定膜是如何被生物相关离子如Ca 2+和Mg 2+干扰的。已知带负电荷的脂质与这些离子强烈相互作用。细胞有多种机制来严格控制离子浓度。预计这些离子会破坏脂质之间局部相互作用的平衡并改变膜特性。3.这个项目将研究蛋白质拥挤在干扰脂质-脂质相互作用中的作用。生物膜中充满了蛋白质。高达20%的膜面积被蛋白质占据，这意味着脂质不仅与其他脂质相互作用，而且与蛋白质侧链相互作用。该团队将研究蛋白质的存在如何改变脂质-脂质相互作用。该奖项反映了NSF的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

Biological membranes are more than barriers between cell compartments. These highly complex environments play a central role in a wide range of functions, including energy production, sensing, and communication. Structure on every length scale is a hallmark of biology, and cell membranes are no exception. Membranes contain hundreds of unique lipids organized on a nanometer length scale, and this organization is critical for cellular function. Abnormal lipid distributions have been linked to cell diseases. This project will investigate the local geometries, environments, and dynamics that dictate the membrane architecture and how membrane architecture relates to biological function. The PI is actively involved in undergraduate and high school student researcher programs: NSF REU, Moncrief Summer Internship, and Welch Summer Scholars Programs and will embark on a recruiting campaign to increase the number of underrepresented students enrolled in the graduate program at UT-Austin. This project will provide an excellent platform for training visiting students who join PI's research group. This will involve visits to Hispanic-serving Institutions in Texas and across the Southwest to advertise the program, network with faculty, and advise students on assembling competitive graduate school applications.In this project, the research team will investigate multiple aspects of heterogeneous membranes using a combination of vibrational spectroscopy and enhanced-sampling molecular dynamics simulations. The following aspects of membranes will be the primary focus of the project: 1. The team will characterize how individual lipid species sample a different range of local environments in a mixture with other lipids, as opposed to single-component, uniform bilayers, which are commonly used as biophysical models. For these reasons, this project seeks to establish a molecular-level view of lipid interactions to inform the importance of membrane diversity, and what specific interactions are not captured by the models. 2. The team will determine how membranes are perturbed by biologically-relevant ions such as Ca2+, and Mg2+. Negatively-charged lipids are known to interact strongly with these ions. Cells have multiple mechanisms to tightly control ion concentrations. These ions are predicted to disrupt the balance of local interactions among lipids and alter membrane properties. 3. This project will examine the role of protein crowding in perturbing lipid-lipid interactions. Biological membranes are packed with proteins. Up to 20% of the membrane area is occupied by proteins, which implies that lipids not only interact with other lipids but also with protein sidechains. The team will investigate how lipid-lipid interactions are modified by the presence of proteins.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.