Functional Biomembrane Architectures in Mesoporous Materials

介孔材料中的功能生物膜结构

• 批准号: 1806366
• 负责人: Marjorie Longo
• 金额: $ 50万
• 依托单位: University of California-Davis
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-07-01 至 2022-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1806366&HistoricalAwards=false
• 关键词: Functional; Biomembrane; Architectures; Mesoporous; Materials

NON-TECHNICAL SUMMARYThe goal of this project is to incorporate biological membrane materials into mesoporous (5-50 nm pores) gel materials to be used for discovery of new medicines, energy generation, and efficient delivery of medicine to the body. Biological membranes serve as biological workhorses by hosting proteins that serve as receptors, channels, transporters, enzymes, and produce energy as long as the proteins remain embedded in biological membrane hosts. Similarly, mesoporous inorganic and organic gels and glasses are workhorses of modern technology yielding unique porosity, photochemical, optical, and catalytic properties. In this project, improved biomaterials will be produced by combining the properties of biological membranes and membrane proteins with the unique properties of mesoporous gel materials. The properties of these new biomaterials will be studied by challenging biophysical and materials characterization, important from a scientific standpoint of unstudied biological organic/inorganic interfaces as well as toward imagining and optimizing any future applications. The proposed activities will provide engineering students with training in biotechnology and biomaterials, recruit a diverse pool of graduate and undergraduate students, provide for exchange of ideas at an international level by organization of an international workshop, and engage freshman and undergraduate engineers via seminars and mentored teaching experiences.TECHNICAL SUMMARY A goal of this proposal will be to implement a novel approach to encapsulate integral membrane proteins (IMPs) into silica- and titania-based mesoporous sol-gels in order to make and study better materials that combine the properties of functional integral membrane proteins (receptor-ligand interactions and ion pumping) with the unique properties of sol-gel materials (high porosity and photocatalysis, respectively). Characterization of these composite mesoporous biomaterials by in-situ methods will be used to study the influence of sol-gel chemistry and nano-confinement details on IMP structure, function, dynamics, and environment. Another goal of this proposal will be to leverage findings and experience in developing pH and crowding-triggered membrane architectures to engineer and study endosomal compartment escape strategies for mesoporous silica nanoparticles (MSNs) as drug delivery vehicles. The proposed strategies provide opportunities to characterize and study the influence of a mesoporous surface on the dynamic and thermodynamic behavior of a membrane and associated proteins and examine the molecular mechanism of endosomal escape. Engineering undergraduates and graduate students working toward these goals will receive valuable interdisciplinary training in new cell biological and genetic engineering techniques, i.e. cell free expression, in the context of production of functional biocomposite sol-gel derived materials. This project will involve organization of an international workshop, creation of a freshman seminar that introduces concepts of biomaterials through study of food, mentoring of an undergraduate team to make a screening platform, and mentored teaching experiences for engineering undergraduates.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.

非技术总结该项目的目标是将生物膜材料纳入介孔（5-50 nm孔）凝胶材料中，用于发现新药，能源生产和有效地将药物输送到体内。 生物膜通过容纳充当受体、通道、转运蛋白、酶的蛋白质而充当生物主力，并且只要蛋白质保持嵌入在生物膜宿主中就产生能量。 同样，中孔无机和有机凝胶和玻璃是现代技术的主力，产生独特的孔隙率，光化学，光学和催化性能。 在该项目中，将通过将生物膜和膜蛋白的性质与介孔凝胶材料的独特性质相结合来生产改进的生物材料。 这些新生物材料的特性将通过挑战生物物理和材料表征来研究，从未研究的生物有机/无机界面的科学观点以及想象和优化任何未来应用的角度来看，这一点很重要。 拟议的活动将为工程专业学生提供生物技术和生物材料方面的培训，招收各种研究生和本科生，通过组织国际讲习班在国际一级交流思想，并通过研讨会和指导教学经验来吸引新生和本科生工程师。技术概述本提案的目标是实现一种新的方法来封装集成将膜蛋白（IMP）引入到二氧化硅和二氧化钛基介孔溶胶-凝胶中，以制备和研究更好的材料，该材料将功能性完整膜蛋白的性质（受体-配体相互作用和离子泵送）与溶胶-凝胶材料的独特性质（分别为高孔隙率和高渗透性）结合联合收割机。 通过原位方法表征这些复合介孔生物材料将用于研究溶胶-凝胶化学和纳米限制细节对IMP结构，功能，动力学和环境的影响。 该提案的另一个目标是利用开发pH和拥挤触发膜结构的发现和经验，设计和研究介孔二氧化硅纳米颗粒（MSN）作为药物递送载体的内体隔室逃逸策略。 所提出的策略提供了表征和研究介孔表面对膜和相关蛋白质的动力学和热力学行为的影响的机会，并研究了内体逃逸的分子机制。 致力于这些目标的工程本科生和研究生将在新的细胞生物学和基因工程技术方面接受宝贵的跨学科培训，即在功能性生物复合材料溶胶-凝胶衍生材料生产的背景下无细胞表达。 该项目将包括组织国际研讨会，创建新生研讨会，通过食品研究介绍生物材料的概念，指导本科生团队制作筛选平台，并指导工程本科生的教学经验。该奖项反映了NSF的法定使命，并通过使用基金会的智力价值和更广泛的影响审查标准进行评估，被认为值得支持。

项目成果

Supplementary Material Structure Retention of Silica Gel-Encapsulated Bacteriorhodopsin in Purple Membrane and in Lipid Nanodiscs

紫膜和脂质纳米盘中硅胶封装的细菌视紫红质的补充材料结构保留

• 发表时间: 2020
• 期刊: Colloids and surfaces
• 作者: Sukriti Gakhar, Subhash H.

Structure retention of silica gel-encapsulated bacteriorhodopsin in purple membrane and in lipid nanodiscs

• DOI: 10.1016/j.colsurfb.2019.110680
• 发表时间: 2020-02-01
• 期刊: COLLOIDS AND SURFACES B-BIOINTERFACES
• 影响因子: 5.8
• 作者: Gakhar, Sukriti;Risbud, Subhash H.;Longo, Marjorie L.
• 通讯作者: Longo, Marjorie L.

Holistic engineering of cell-free systems through proteome-reprogramming synthetic circuits

• DOI: 10.1038/s41467-020-16900-7
• 发表时间: 2020-06-19
• 期刊: NATURE COMMUNICATIONS
• 影响因子: 16.6
• 作者: Contreras-Llano, Luis E.;Meyer, Conary;Tan, Cheemeng
• 通讯作者: Tan, Cheemeng

Supplementary Material for Hybrid lipid/block copolymer vesicles display broad phase coexistence region

混合脂质/嵌段共聚物囊泡的补充材料显示宽相共存区域

• 发表时间: 2021
• 期刊: Biochimica et biophysica acta
• 作者: Hamada, Naomi;Gakhar, Sukriti;Longo, Marjorie L.
• 通讯作者: Longo, Marjorie L.

Hybrid lipid/block copolymer vesicles display broad phase coexistence region

杂化脂质/嵌段共聚物囊泡显示出宽相共存区域

• DOI: 10.1016/j.bbamem.2021.183552
• 发表时间: 2021
• 期刊: Biochimica et Biophysica Acta (BBA
• 作者: Hamada, Naomi;Gakhar, Sukriti;Longo, Marjorie L.
• 通讯作者: Longo, Marjorie L.