Collaborative Research: Active Transport of Lipid Vesicles in Osmotic Gradients

合作研究：渗透梯度下脂质囊泡的主动运输

• 批准号: 1952295
• 负责人: Manish Kumar
• 金额: $ 4.33万
• 依托单位: University of Texas at Austin
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-08-27 至 2021-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1952295&HistoricalAwards=false
• 关键词: Collaborative; Research; Active; Transport; Lipid

The membranes of living cells are highly and selectively permeable to water. Variations in the osmotic pressure due to dissolved molecules drives water transport across the membrane, thereby inducing fluid flows and membrane motions. Such flows are critical to biological processes such as the regulation of cell water content, the transport of intra- and extracellular compartments, and the migration of cells in tissues. Despite their importance, the fundamental fluid mechanics underlying these processes remains poorly understood. This project aims to advance our understanding of fluid flows and membrane motions driven by osmotic gradients. Such knowledge will further enable biotechnologies involving the extraction, separation, and delivery of extracellular vesicles, which are actively pursued as diagnostic and therapeutic tools for treating human diseases. The project will also provide educational opportunities to middle and high school students from underrepresented groups through laboratory tours and summer research experiences.The central goal of the research is to develop experimental platforms and theoretical models that elucidate the physical mechanisms underlying the motion of lipid vesicles in osmotic gradients ? a process called osmophoresis. Using microfluidic systems, the research will quantify vesicle velocity as a function of membrane properties such as vesicle size, permeability, rigidity, tension / excess area, and surface charge as well as environmental properties such as solute type, gradient magnitude, fluid viscosity, and confinement. Notably, the project will use lipid membranes incorporating aquaporin water channels to create high permeability vesicles that mimic native exosomes. The experiments will provide definitive data with which to enhance our understanding of osmophoresis and its impact on vesicle transport in biology. The proposed theory will integrate previous work on the osmophoresis of rigid spherical membranes with models of membrane dynamics that account for deformation and flow within incompressible lipid bilayers. The theoretical investigations will ultimately reproduce and explain experimental observations of rapid vesicle motions in osmotic gradients. Finally, the demonstration of osmophoretic vesicle sorting will provide a fundamental basis for biotechnologies involving the separation and characterization of extracellular vesicles.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.

活细胞的膜高度可渗透到水中。由于溶解分子而引起的渗透压的变化驱动跨膜的水传输，从而诱导流体流和膜运动。这种流对于生物学过程至关重要，例如细胞水含量的调节，细胞内和细胞外室的运输以及组织中细胞的迁移。尽管它们的重要性，但这些过程基础的基本流体机制仍然很少理解。该项目旨在提高我们对渗透梯度驱动的流体流和膜运动的理解。这些知识将进一步实现涉及细胞外囊泡提取，分离和传递的生物技术，这些囊泡被积极地作为治疗人类疾病的诊断和治疗工具。该项目还将通过实验室参观和夏季研究经验为来自代表性不足的小组的中学和高中生提供教育机会。该研究的核心目标是开发实验平台和理论模型，以阐明在渗透梯度中脂质囊泡运动的物理机制？一个称为渗透态的过程。使用微流体系统，该研究将量化囊泡速度与膜特性（例如囊泡尺寸，渗透率，刚度，张力 /过量面积以及表面电荷）以及溶质类型，梯度尺度，流体粘度和限制等环境特性的函数。 值得注意的是，该项目将使用结合水通道水通道的脂质膜来产生模仿天然外泌体的高渗透囊泡。这些实验将提供明确的数据，以增强我们对渗透压及其对生物学囊泡运输的影响。提出的理论将将刚性球形膜渗透压的先前工作与膜动力学模型相结合，这些模型解释了不可压缩的脂质双层中的变形和流动。理论研究最终将繁殖并解释渗透梯度快速囊泡运动的实验观察结果。最后，渗透囊泡排序的演示将为涉及涉及细胞外囊泡分离和表征的生物技术提供基本基础。该奖项反映了NSF的法定任务，并被认为是值得通过基金会的知识分子和更广泛影响的审查标准来通过评估来通过评估来支持的。

项目成果

Rapid fabrication of precise high-throughput filters from membrane protein nanosheets

• DOI: 10.1038/s41563-019-0577-z
• 发表时间: 2020-01
• 期刊: Nature Materials
• 影响因子: 41.2
• 作者: Yu-Ming Tu;Woochul Song;Tingwei Ren;Yue-xiao Shen;Ratul Chowdhury;P. Rajapaksha;Tyler E. Culp;Laxmicharan Samineni;Chao Lang;Alina Thokkadam;Drew Carson;Yuxuan Dai;A. Mukthar;Miao Zhang;A. Parshin;Janna N. Sloand;Scott H. Medina;M. Grzelakowski;Dibakar Bhattacharya;W. Phillip;E. Gomez;R. Hickey;Yi-Min Wei;Manish Kumar

Prospective applications of nanometer-scale pore size biomimetic and bioinspired membranes

• DOI: 10.1016/j.memsci.2020.118968
• 发表时间: 2020-12
• 期刊: Journal of Membrane Science
• 影响因子: 9.5
• 作者: Yu-Ming Tu;Laxmicharan Samineni;Tingwei Ren;A. Schantz;Woochul Song;Siddhartha Sharma;Manish Kumar

Beyond Aquaporins: Recent Developments in Artificial Water Channels

超越水通道蛋白：人工水道的最新进展

• DOI: 10.1021/acs.langmuir.2c01605
• 发表时间: 2022
• 期刊: Langmuir
• 影响因子: 3.9
• 作者: Song, Woochul;Kumar, Manish
• 通讯作者: Kumar, Manish

Artificial water channels enable fast and selective water permeation through water-wire networks

• DOI: 10.1038/s41565-019-0586-8
• 发表时间: 2019-12
• 期刊: Nature Nanotechnology
• 影响因子: 38.3
• 作者: Woochul Song;Himanshu Joshi;Ratul Chowdhury;Joseph S. Najem;Yue-xiao Shen;Chao Lang;Codey B. Henderson;Yu-Ming Tu;Megan Farell;Megan E. Pitz;C. Maranas;P. Cremer;R. Hickey;Stephen A. Sarles;Jun‐Li Hou;A. Aksimentiev;Manish Kumar