Rotational Drift-Diffusion of Proteins in Dynamic Bilayer Lipid Membranes

动态双层脂质膜中蛋白质的旋转漂移扩散

• 批准号: 1951728
• 负责人: Yongcheng Zhou
• 金额: $ 19.23万
• 依托单位: Colorado State University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-06-01 至 2024-05-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1951728&HistoricalAwards=false
• 关键词: Rotational; Drift; Diffusion; Proteins; Dynamic

Surrounding living cells and many subcellular compartments are membranes, which allow the passage of certain information and materials but block some others. Membranes deform at different magnitudes, sometimes drastically, during this selective transport, and the processes are facilitated and regulated by various protein complexes. Proteins accomplish regulation through attaching to or residing in membranes at specific locations. Understanding and quantifying the number and orientation of these membrane proteins on dynamically deforming membranes is essential for developing medications and therapeutic strategies to facilitate or suppress membrane transport. By integrating mathematical modeling and computational simulations, this research will examine (1) how the rotation and translation of proteins leads to the deformation of bilayer membranes; (2) how deformation leads proteins to stay at specific positions and orientations; and (3) how these interactions are related to protein structure and membrane composition. This investigation aims to provide reliable models and efficient algorithms for protein-membrane interactions and related biomedical applications.The bilayer membranes in cells are highly dynamic, heterogeneous environments with multiple critical biological functions, many of which are regulated by specific proteins through various protein-membrane interactions. The rotational and translational localizations of membrane proteins are the major driving mechanism of membrane morphological changes. Yet quantification of these localizations in dynamical bilayer membranes remains mathematically and computationally challenging. This research strives to introduce principal directions and curvature to account for orientation-dependent localization in membranes and the resulting membrane deformation. Surface drift-diffusion equations with integer and fractional orders will be derived for low and high protein densities. Through integrating mathematical and computational investigation of these equations, the research will generate a predictive model for the dynamics of bilayer membranes with surface protein flows.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.

周围的活细胞和许多亚细胞室是膜，可以通过某些信息和材料传递，但会阻止其他一些信息。 在这种选择性运输过程中，膜在不同的幅度（有时有时会急剧）变形，并且过程促进并受到各种蛋白质复合物的调节。蛋白质通过附着在特定位置的膜上或居住在膜上来完成调节。了解和量化这些膜蛋白在动态变形膜上的数量和方向对于开发药物和治疗策略至关重要，以促进或抑制膜运输。通过整合数学建模和计算模拟，这项研究将检查（1）蛋白质的旋转和翻译如何导致双层膜的变形； （2）变形如何导致蛋白质保持在特定位置和方向； （3）这些相互作用如何与蛋白质结构和膜组成有关。 这项研究旨在为蛋白质 - 膜相互作用和相关的生物医学应用提供可靠的模型和有效算法。细胞中的双层膜是高度动态的，具有多种关键生物学功能的异质性异构性环境，其中许多环境通过各种蛋白质 - 膜膜相互作用来调节，许多膜受到特定蛋白质的调节。膜蛋白的旋转和翻译位置是膜形态变化的主要驱动机制。然而，对动态双层膜中这些局部化的定量在数学上和计算上仍然具有挑战性。这项研究致力于引入主要方向和曲率，以说明膜中的方向依赖性定位以及所得的膜变形。具有整数和分数顺序的表面漂移扩散方程将用于低蛋白质密度和高蛋白质。通过将这些方程式的数学和计算研究整合在一起，该研究将为双层膜的动力学产生一个预测模型，以表面蛋白质流动。这项奖项反映了NSF的法定任务，并被认为是值得通过基金会的知识分子优点和更广泛影响的审查标准来通过评估来支持的。