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

• 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

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微调的能力。这项研究磁辅助自组装用于快速2D膜蛋白结晶的奖项将支持对这些膜蛋白以及更广泛的生物材料磁性的基础研究。PI将利用他们对膜蛋白在磁场中行为的知识来支持从这些生物材料开发二维晶体。最后，这些晶体将被部署在高度选择性传感和分离应用的设备中。同时，该项目将资助本科生研究培训和指导计划的扩展，其中包括为本科生博士生导师提供的3小时正式培训过程，为即将到来的本科生研究人员提供的正式目标设定过程，以及为本科生、博士导师和PI进行的360度评估过程，每两个月进行一次，并在项目完成后进行。技术PI建议研究在磁场存在下膜蛋白(MP)自组装的基础物理和化学，以便为在大范围内实现高结晶有序的MPS的可扩展2D结晶提供策略。他们将计算MPS和支持基质(嵌段共聚物和脂类)的抗磁性，以评估这项技术在已知MPS上的普适性，并为后续的自组装模拟提供信息。发展了一种新的粗晶模型来描述MP晶体在外加磁场存在和不存在时的自组装。该模型将充分有效地作为前端生物材料制造设计工具，跨越MPS和支持基质的不同组合。PIS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，将测试OmpF和PhR的2D MP晶体作为筛选配体和阻滞剂的模型系统，并与当前最先进的双层类型系统进行比较。这项工作将有助于1)计算大分子的抗磁各向异性和抗磁磁化率的新方法，其中一级、二级和三级结构都对分子的磁性有贡献，2)物理上理解驱动自组装动力学和最终状态的各种相互竞争的力，3)一个指导2D MP晶体制造的实验设计的建模工具，以及4)2D MP晶体在功能器件中的演示和相对于当前技术水平的性能评估。

项目成果

Competing Ion Behavior in Direct Electrochemical Selenite Reduction

• DOI: 10.1021/acsestengg.1c00099
• 发表时间: 2021-04
• 期刊: 2006 IEEE International Symposium on Signal Processing and Information Technology
• 作者: S. Zou;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
• 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.

Direct Electrochemical Pathways for Selenium Reduction in Aqueous Solutions

• DOI: 10.1021/acssuschemeng.0c06585
• 发表时间: 2021-01
• 期刊: ACS Sustainable Chemistry & Engineering
• 影响因子: 8.4
• 作者: S. Zou;M. Mauter

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
• 期刊: ACS Applied Materials & Interfaces
• 影响因子: 9.5
• 作者: Radvar, Elham;Shi, Yejiao;Grasso, Salvatore;Edwards-Gayle, Charlotte J.;Liu, Xitong;Mauter, Meagan S.;Castelletto, Valeria;Hamley, Ian W.;Reece, Michael J.;S. Azevedo, Helena
• 通讯作者: S. Azevedo, Helena