EAGER: (ST1) Dissipative Self-Assembly of Metabolic Soft Matter

EAGER：（ST1）代谢软物质的耗散自组装

• 批准号: 1938303
• 负责人: Kyle Bishop
• 金额: $ 30万
• 依托单位: Columbia University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-08-15 至 2022-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1938303&HistoricalAwards=false
• 关键词: EAGER; ST1; Dissipative; Self; Assembly

Non-technical Abstract"Humans can survive in hostile environments by building compartments (e.g., houses) and creating favorable conditions within their interiors (e.g., by heating or cooling). Similarly, living cells use material compartments and biochemical reactions to enable their proper function in diverse environments. These functions -such as the ability to move, adapt, heal, and communicate- derive from the close integration of material structures and chemical processes. The ability to synthesize "metabolic materials" with similar functionality remains extremely limited. It is known how to make material structures and how to control systems of chemical reactions. However, it is not known how to couple the two together to animate matter with flows of energy and information as living organisms do. To address this challenge, this project will create relatively simple material systems in which molecular compartments are coupled to chemical reactions by engineered feedback loops. It will demonstrate how such chemically-fueled metabolic materials can enable new functions such as the ability to assemble in hostile environments, to control size and morphology, to regulate fuel consumption, and to degrade on demand. The basic principles identified will guide the future realization of other chemically-fueled material systems inspired by living matter.Technical AbstractThis project proposes to create "metabolic soft matter" based on self-assembled polymeric compartments with primitive metabolic activity that modify their local environment to stabilize (or destabilize) the assembled structures. Metabolic activity is introduced by the co-assembly of supercharged enzymes into coacervate droplets formed by liquid-liquid phase separation of oppositely charged polyelectrolytes in water. In the presence of chemical "fuel", these enzymes catalyze reactions that alter the local conditions (e.g., pH) and thereby droplet stability. Importantly, the processes of self-assembly and metabolism are mutually dependent and allow for engineering both positive and negative feedback loops. Self-assembly enhances metabolic activity by concentrating enzymes within small volumes, thereby increasing the local concentration of metabolic product(s). Reaction-induced concentration changes serve to enhance or inhibit self-assembly depending on the choice of materials and reactions. Building on designed metabolic materials based on supercharged catalase that respond to pH changes driven by the decomposition of H2O2 fuel - this proposed work aims (1) to engineer the pH-dependent phase behavior of coacervate drops enriched with supercharged enzymes; (2) to quantify metabolic activity and its influence in modifying the drop environment; and (3) to couple metabolism and self-assembly using positive and negative feedback to enable dynamic functions.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.

非技术抽象的“人类可以通过建筑室（例如房屋）（例如房屋）并在其内部（例如，通过加热或冷却）在敌对环境中生存。同样，活细胞同样，活细胞使用材料隔室和生物化学反应来启用其适当的功能，以使其在各种功能中延伸，并适应这些功能，并适应了这些功能。过程。 它将证明这种化学燃料的代谢材料如何使新功能（例如在敌对环境中组装，控制尺寸和形态，调节燃油消耗并按需降解）等新功能。 所确定的基本原理将指导其他受生物启发的其他化学燃料材料系统的未来实现。技术抽象该项目建议基于具有原始代谢活性的自组装聚合物隔室创建“代谢软质”，以修改其本地环境以稳定（或稳定）组合结构。 代谢活性是由增压酶的共组合到水中液体液相分离形成的凝聚液液滴中的。 在存在化学“燃料”的情况下，这些酶催化了改变局部条件（例如pH）的反应，从而改变了液滴稳定性。重要的是，自组装和新陈代谢的过程是相互依赖的，并且允许进行正面反馈和负反馈循环。 自组装通过将酶浓缩在少量体积中，从而增强了代谢活性，从而增加了代谢产物的局部浓度。 反应诱导的浓度变化有助于增强或抑制自组装，具体取决于材料和反应的选择。 基于设计的代谢材料基于增压过氧化氢酶的响应，该材料响应于H2O2燃料的分解而驱动的pH变化 - 这项提出的工作目的（1）可以（1）来设计含有增压酶的凝聚液滴剂的pH依赖性相行为； （2）量化代谢活性及其在修饰滴环境中的影响； （3）使用积极和负面的反馈来促进动态功能，以夫妇的代谢和自组装为生。该奖项反映了NSF的法定任务，并使用基金会的知识分子优点和更广泛的影响评估标准，被认为值得通过评估来提供支持。