New Strategy for Encapsulating Integral Membrane Proteins

封装完整膜蛋白的新策略

• 批准号: 1500275
• 负责人: Marjorie Longo
• 金额: $ 42万
• 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: 2015
• 资助国家: 美国
• 起止时间: 2015-09-01 至 2018-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1500275&HistoricalAwards=false
• 关键词: New; Strategy; Encapsulating; Integral; Membrane

Non-Technical: The PIs goal is to provide a strategy so that the majority of integral membrane proteins (IMPs) could be routinely encapsulated in the nanometer-sized pores of gels for drug discovery, and biotechnology, and energy generation. IMPs are nanometer-size biological workhorses that produce energy, serve as receptors, channels, transporters, and enzymes, when they are embedded in biological membrane hosts. Similarly, nanoporous gels and glasses are mainstays of modern technology because of their unique photochemical, optical, and catalytic properties. PIs IMP-containing bio-functional gels will combine these unique functionalities: e.g. the gel (for solar energy capture) and the IMP for energy absorption from a broader spectrum of wavelengths. They will study nanolipoprotein particles (NLPs) as the biological membrane hosts of IMPs entrapped in inorganic and organic nanoporous gels. NLPs are disc-shaped 10-25 nanometer-sized lipid bilayer patches stabilized by a belt of scaffold proteins. The NLP approach represents a major breakthrough because NLPs fit precisely into the 5-50 nanometer-sized pores of the gels and NLPs serve as a robust host for any IMP so that all components remain functional. On the training side, engineering undergraduates and graduate students working on this project will gain valuable experience that will prepare them for new careers that integrate materials science with biotechnology. Following previous success the PIs will organize a second international workshop "Biomembrane Frontiers: Nanostructures, Models, and the Design of Life: II". Further, they will publish a Tutorial Review on "Creating and Characterizing Biomembrane/Materials Interfaces". Technical: Integral membrane proteins (IMPs) require a lipid membrane host and carry out a number of useful biological functions that could be harnessed by routine encapsulation in mesoporous sol-gel materials. The PIs will study nanolipoprotein particles (NLPs) as the biological membrane hosts of IMPs entrapped in inorganic and organic mesoporous sol-gels. NLPs are soluble discoidal 10-25 nm-sized particles comprised of a lipid bilayer patch stabilized by a belt of apolipoprotein scaffold proteins that can be formed through in vitro self-assembly. NLPs fit precisely into the 5-50 nm-sized pores of the gels and NLPs serve as robust hosts for IMPs, therefore all components may retain their structures and functions. Exploration of the parameters of nanoscale confinement and chemical environment in relation to dynamics, structure, and function of the NLP and IMP-NLP are important from a scientific standpoint as well as toward imagining and optimizing any future applications. Characterization of these parameters will take place with integrated studies employing state-of-the-art dynamic TEM, electron paramagnetic resonance, NMR, circular dichroism, and fluorimetry. Materials Science and Chemical Engineering undergraduates and graduate students working on this project will receive valuable interdisciplinary training in new cell biological and bioengineering techniques, i.e. cell free expression, in the context of production of a functional biocomposite sol-gel materials. The PIs will organize an international workshop, "Biomembrane Frontiers: Nanostructures, Models, and the Design of Life: II" and publish an Instructional Review on "Creating and Characterizing Biomembrane/Materials Interfaces". In the education arena, PIs will provide special topical freshman seminars on Biomaterials.

非技术：PIS的目标是提供一种策略，以便大多数完整的膜蛋白(IMP)可以常规地被包裹在凝胶的纳米大小的孔中，用于药物发现、生物技术和能源生产。IMP是一种纳米尺寸的生物主力，当它们嵌入到生物膜宿主中时，它们产生能量，充当受体、通道、转运体和酶。同样，纳米多孔凝胶和玻璃由于其独特的光化学、光学和催化性能而成为现代技术的支柱。含有PIS IMP的生物功能凝胶将结合这些独特的功能：例如，凝胶(用于太阳能捕获)和IMP用于从更广泛的波长吸收能量。他们将研究纳米脂蛋白颗粒(NLP)作为包裹在无机和有机纳米孔凝胶中的IMPS的生物膜宿主。NLP是盘状的10-25纳米大小的脂质双层贴片，由一条支架蛋白质带稳定。NLP方法代表着一项重大突破，因为NLP正好适合凝胶的5-50纳米大小的孔隙，并且NLP作为任何IMP的坚固宿主，使所有组件保持功能。在培训方面，从事该项目的工程学本科生和研究生将获得宝贵的经验，为将材料科学与生物技术相结合的新职业做好准备。继以往的成功之后，私营部门将组织第二次“生物膜前沿：纳米结构、模型和生命设计：II”国际研讨会。此外，他们还将出版《创建和表征生物膜/材料界面》的教程评论。技术：完整的膜蛋白(IMPS)需要一个脂质膜宿主，并执行许多有用的生物学功能，这些功能可以通过常规的介孔溶胶-凝胶材料的包埋来实现。PIS将研究纳米脂蛋白颗粒(NLP)作为包裹在无机和有机介孔溶胶中的IMPS的生物膜宿主。NLP是一种可溶的盘状颗粒，大小为10-25 nm，由一条载脂蛋白支架蛋白带稳定的脂质双层贴片组成，可通过体外自组装形成。NLP正好适合凝胶5-50 nm大小的孔，NLP是IMPS的强健宿主，因此所有组分都可以保持其结构和功能。从科学的角度探索纳米尺度的限制和化学环境参数与NLP和IMP-NLP的动力学、结构和功能的关系，对于想象和优化任何未来的应用都是重要的。这些参数的表征将通过使用最先进的动态透射电子显微镜、电子顺磁共振、核磁共振、圆二色谱和荧光法的综合研究来进行。从事这个项目的材料科学和化学工程本科生和研究生将在生产功能性生物复合溶胶-凝胶材料的背景下，接受关于新的细胞生物学和生物工程技术的有价值的跨学科培训，即无细胞表达。PIS将组织一次名为“生物膜前沿：纳米结构、模型和生命设计：II”的国际研讨会，并出版一篇关于“生物膜/材料界面的创建和特征”的教学评论。在教育领域，PIS将提供关于生物材料的特别新生专题研讨会。