Collaborative Research: Magnetically Assisted Self-Assembly for Facile 2D Membrane Protein Crystallization

合作研究：磁力辅助自组装轻松实现二维膜蛋白结晶

基本信息

批准号：
2023833
负责人：
Meagan Mauter
金额：
$ 27.76万
依托单位：
Stanford University
依托单位国家：
美国
项目类别：
Continuing Grant
财政年份：
2019
资助国家：
美国
起止时间：
2019-09-01 至 2022-05-31
项目状态：
已结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=2023833&HistoricalAwards=false
关键词：
Collaborative Research Magnetically Assisted Self

项目摘要

Non-Technical Membrane proteins are cells' primary mechanism for interacting with the external environment, and thus demonstrate exceptionally fine-tuned capabilities in sensing, selective transport, and catalysis. This award to study Magnetically Assisted Self-Assembly for Facile 2D Membrane Protein Crystallization will support fundamental research on the magnetic properties of these membrane proteins, and biological materials more generally. The PIs will leverage their knowledge of membrane protein behavior in magnetic fields to support the development of two-dimensional crystals from these biological materials. Finally, these crystals will be deployed in devices for highly selective sensing and separation applications. In parallel, the project will fund the expansion of an undergraduate research training and mentorship program that includes a formal 3-hour training process for PhD student supervisors of undergraduate students, a formal goal-setting process for incoming undergraduate researchers, and a 360-degree evaluation process for undergraduates, PhD supervisors, and the PI conducted on a bi-monthly basis and upon completion of the project.Technical PIs propose to investigate the fundamental physics and chemistry of membrane protein (MP) self-assembly in the presence of a magnetic field to inform strategies for scalable 2D crystallization of MPs with high crystalline order realized over large areas. They will compute the diamagnetic susceptibility of MPs and supporting matrices (block co-polymers and lipids) to assess the generalizability of this technique across known MPs and to inform subsequent self-assembly simulations. A novel coarse-grain model will be developed to describe the self-assembly of MP crystals in the presence and absence of an applied magnetic field. This model will be sufficiently efficient as to serve as a front-end biomaterial fabrication design tool across diverse combinations of MPs and supporting matrices. PIs will validate these models by experimentally characterizing the effect of magnetic fields on MP crystallization under diverse experimental conditions. Finally, 2D MP crystals of OmpF and pHR will be tested as model systems for screening ligands and blockers in comparison with current state-of-the-art bilayer type systems. This work will contribute 1) a novel approach for computing the diamagnetic anisotropy and diamagnetic susceptibility of large molecules in which primary, secondary, and tertiary structure each contribute to the magnetic properties of the molecule, 2) a physical understanding of the various competing forces that drive the kinetics and final state of self-assembly, 3) a modeling tool to guide experimental design for the fabrication of 2D MP crystals, and 4) a demonstration of 2D MP crystals in functional devices and an assessment of their performance relative to the current state-of-the-art.

非技术性膜蛋白是细胞与外部环境相互作用的主要机制，因此在传感、选择性运输和催化方面表现出异常精细的能力。该奖项旨在研究磁力辅助自组装以实现简单的二维膜蛋白结晶，将支持对这些膜蛋白以及更广泛的生物材料的磁性的基础研究。 PI 将利用他们对磁场中膜蛋白行为的了解来支持利用这些生物材料开发二维晶体。最后，这些晶体将被部署在用于高选择性传感和分离应用的设备中。与此同时，该项目将资助扩大本科生研究培训和指导计划，其中包括为本科生的博士生导师提供正式的 3 小时培训过程、为即将入学的本科生研究人员提供正式的目标设定过程以及 360 度全方位培训对本科生、博士生导师和 PI 的评估过程每两个月进行一次，并在项目完成后进行。技术 PI 建议研究磁性存在下膜蛋白 (MP) 自组装的基础物理和化学字段通知在大面积上实现具有高晶序的 MP 的可扩展二维结晶策略。他们将计算 MP 和支持基质（嵌段共聚物和脂质）的抗磁化率，以评估该技术在已知 MP 中的普遍性，并为后续的自组装模拟提供信息。将开发一种新颖的粗粒模型来描述在存在和不存在外加磁场的情况下 MP 晶体的自组装。该模型将足够有效，可以作为跨 MP 和支持基质的不同组合的前端生物材料制造设计工具。 PI 将通过实验表征不同实验条件下磁场对 MP 结晶的影响来验证这些模型。最后，OmpF 和 pHR 的 2D MP 晶体将作为模型系统进行测试，用于筛选配体和阻断剂，并与当前最先进的双层类型系统进行比较。这项工作将贡献 1) 一种计算大分子抗磁各向异性和抗磁磁化率的新方法，其中一级、二级和三级结构各自对分子的磁性有贡献，2) 对影响分子磁性的各种竞争力的物理理解驱动自组装的动力学和最终状态，3) 指导 2D MP 晶体制造实验设计的建模工具，以及 4) 功能器件中 2D MP 晶体的演示和评估他们的性能相对于当前最先进的水平。

项目成果

期刊论文数量（5）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Competing Ion Behavior in Direct Electrochemical Selenite Reduction

DOI：
10.1021/acsestengg.1c00099
发表时间：
2021-04-22
期刊：
2006 IEEE International Symposium on Signal Processing and Information Technology
影响因子：
0
作者：
S. Zou;M. Mauter
通讯作者：
M. Mauter

Inadequacy of current approaches for characterizing membrane transport properties at high salinities

当前表征高盐度下膜传输特性的方法的不足

DOI：
10.1016/j.memsci.2022.121246
发表时间：
2023-02
期刊：
Journal of Membrane Science
影响因子：
9.5
作者：
Liang, Yuanzhe;Dudchenko, Alexander V.;Mauter, Meagan S.
通讯作者：
Mauter, Meagan S.

Magnetic Field-Induced Alignment of Nanofibrous Supramolecular Membranes: A Molecular Design Approach to Create Tissue-like Biomaterials

磁场诱导的纳米纤维超分子膜排列：一种创建组织样生物材料的分子设计方法

DOI：
10.1021/acsami.0c05191
发表时间：
2020-05
期刊：
ACS Applied Materials & Interfaces
影响因子：
9.5
作者：
Radvar, Elham;Shi, Yejiao;Grasso, Salvatore;Edwards;Liu, Xitong;Mauter, Meagan S.;Castelletto, Valeria;Hamley, Ian W.;Reece, Michael J.;S. Azevedo, Helena
通讯作者：
S. Azevedo, Helena

Microporous Polyethersulfone Membranes Grafted with Zwitterionic Polymer Brushes Showing Microfiltration Permeance and Ultrafiltration Bacteriophage Removal

接枝两性离子聚合物刷的微孔聚醚砜膜显示出微滤渗透性和超滤噬菌体去除效果

DOI：
10.1021/acsami.3c01495
发表时间：
2023-04
期刊：
ACS Applied Materials & Interfaces
影响因子：
9.5
作者：
Qin, Ji;Ziemann, Eric;Bar;Bone, Sharon E.;Liang, Yuanzhe;Mauter, Meagan S.;Herzberg, Moshe;Bernstein, Roy
通讯作者：
Bernstein, Roy

Direct Electrochemical Pathways for Selenium Reduction in Aqueous Solutions

水溶液中硒还原的直接电化学途径