Bioengineering and Molecular Simulation of Membrane Fusion Processes and Mechanisms

本研究旨在将表征细胞膜高分辨率结构的工具与先进的原子学和统计计算机模型相结合，以确定钙离子在膜融合过程中的作用。该方案的主要假设是，钙离子的存在可以通过连接相对外膜的磷脂头基来减少相对双层之间的静电斥力，从而促进膜的融合。该项目将在脂质体形式的真实脂膜中使用模拟和实验。其具体目标是：(1)确定水合钙离子与相对双层膜上的磷脂头基之间以及同一膜上磷脂头基之间的可能相互作用，(2)评估由于钙离子的存在而引起的相对双层之间的变化，(3)评估钙离子对膜相关蛋白(t-/v-SNARE)结合作用的作用，以及(4)为学生提供本科生和研究生的研究经验。细胞融合的过程对于正常的细胞功能和异常的细胞事件是非常重要的，例如药物输送(好事)或病原体攻击(坏事)。因此，了解钙离子在这一机制中的确切作用将对广泛的基础和实际问题大有裨益。本科生和研究生将参与其中。

0730768PotoffThis research aims to combine tools for characterizing the high-resolution structures of cell membranes, with advanced atomistic and statistical computer modeling, to determine the role of calcium ions in the membrane fusion process. The main hypothesis of the proposal is that the presence of calcium ions can reduce electrostatic repulsion between opposing bilayers by bridging the phospholipid headgroups of the opposing outer membrane layers and, therefore, promoting membrane fusion. The project will use both simulations and experiments in real lipid membranes in the form of liposomes. The specific aims are: (1) determination of possible interactions between hydrated calcium ions and phospholipid headgroups of opposing bilayer membranes and also between phospholipids headgroups on the same membrane, (2) evaluation of the alterations between opposing bilayers that are caused by the presence of calcium cations, (3) evaluation of the role of calcium cations on the binding interactions between membrane associated proteins (t-/v-SNAREs), and (4) to provide undergraduate and graduate research experience for students. The process of cell fusion is very important to normal cellular function, and to abnormal cell events, such as drug delivery (a good thing) or pathogen attack (a bad thing). Understanding the precise role of calcium ions in this mechanism would, therefore, be of great benefit to a broad range of fundamental and practical matters. Undergraduate and graduate students will be involved.