ISS: Protein flow and gelation in the absence of solid-wall nucleation

ISS：在没有固壁成核的情况下蛋白质流动和凝胶化

• 批准号: 2323020
• 负责人: Amir Hirsa
• 金额: $ 45.28万
• 依托单位: Rensselaer Polytechnic Institute
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-01 至 2026-07-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2323020&HistoricalAwards=false
• 关键词: ISS; Protein; flow; gelation; absence

Proteins are large, flexible macromolecules that perform a vast range of functions within living organisms, small and large. Their functions span from copying genetic material to providing structural integrity to cells and organisms. Because of their size, flexibility, and biochemistry, proteins can undergo structural changes that dictate their function, or sometimes cause disease. The ability to understand and predict how the conditions that proteins experience affect their structure and conformation, and in turn their functioning in solution, is very important. This award will be used for the development of predictive models for both fundamental science and industry, including development of first-principle models and manufacturing of pharmaceuticals. Microgravity makes it possible to study how protein solutions flow without complications associated with the interaction of protein solutions and solid walls. This project utilizes the microgravity environment of the International Space Station, where surface tension becomes a dominant force; this allows the study of protein solutions in the ring-sheared drop module, a container-less biochemical reactor. The purpose of this award is to gain deeper scientific understanding of protein association, aggregation, and gelation in systems with high protein concentration in the presence of free surfaces. The ring-sheared drop module aboard the International Space Station was designed for studying flows in gas-liquid systems, in which surface tension provides containment and shear is conveyed primarily through the action of surface shear viscosity. The ring-sheared drop is especially suitable for studying protein rheology as it minimizes any wall-nucleation effects. This project targets multiple classes of proteins, including globular, hormonal, and monoclonal antibody therapeutics. The recent development of protein solution viscosity models from first principles will be utilized as a foundation for mechanistic models including coupling of interfacial and bulk stresses to predict the flow of protein solutions. Variables captured by the model include the protein type (e.g., transport, hormone, or antibody), physical state (e.g. monomers, aggregates, fibrils, or gels), and concentration. Predictions from these models will be tested in the ring-sheared drop aboard the International Space Station.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.

蛋白质是大的，灵活的大分子，在生物体内执行广泛的功能，小的和大的。它们的功能从复制遗传物质到为细胞和生物体提供结构完整性。由于它们的大小，灵活性和生物化学，蛋白质可以经历决定其功能的结构变化，有时甚至导致疾病。 理解和预测蛋白质所经历的条件如何影响其结构和构象，进而影响其在溶液中的功能的能力非常重要。该奖项将用于基础科学和工业预测模型的开发，包括第一原理模型的开发和药品的生产。微重力使研究蛋白质溶液如何流动成为可能，而不会出现与蛋白质溶液和固体壁相互作用相关的复杂情况。该项目利用了国际空间站的微重力环境，其中表面张力成为主导力;这使得能够在环剪切滴模块（无容器生化反应器）中研究蛋白质溶液。 该奖项的目的是在自由表面存在的情况下，对高蛋白质浓度系统中的蛋白质缔合、聚集和凝胶化有更深入的科学理解。国际空间站上的环形剪切液滴模块是为研究气液系统中的流动而设计的，在气液系统中，表面张力提供了密封，剪切主要通过表面剪切粘度的作用来传递。环剪切液滴特别适用于研究蛋白质流变学，因为它最大限度地减少了任何壁成核效应。该项目针对多种类型的蛋白质，包括球状，激素和单克隆抗体治疗。蛋白质溶液粘度模型的第一原理的最新发展将被用作机械模型的基础，包括界面和体积应力的耦合，以预测蛋白质溶液的流动。模型捕获的变量包括蛋白质类型（例如，运输、激素或抗体）、物理状态（例如单体、聚集体、原纤维或凝胶）和浓度。这些模型的预测结果将在国际空间站上的环剪落中进行测试。该奖项反映了NSF的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。