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

非技术摘要“人类可以通过建造隔间（例如，房屋）并在其内部创造有利条件（例如，通过加热或冷却）。 类似地，活细胞使用物质隔室和生化反应来使它们在不同的环境中发挥适当的功能。 这些功能--如移动、适应、愈合和交流的能力--源自物质结构和化学过程的紧密结合。 合成具有类似功能的“代谢材料”的能力仍然极其有限。 人们知道如何制造材料结构和如何控制化学反应系统。 然而，目前还不知道如何将两者结合在一起，使物质像生物体那样具有能量和信息流。 为了应对这一挑战，该项目将创建相对简单的材料系统，其中分子隔室通过工程反馈回路与化学反应耦合。 它将展示这种化学燃料代谢材料如何实现新的功能，例如在恶劣环境中组装的能力，控制尺寸和形态，调节燃料消耗以及按需降解。 确定的基本原则将指导未来实现其他化学燃料材料系统的启发living matter.Technical AbstractThis project proposed to create“metabolic soft matter”based on self-assembled polymer compartments with primitive metabolic activity that modify their local environment to stabilize（or disabilize）the assembled structures. 代谢活性通过超电荷酶的共组装引入凝聚液滴中，所述凝聚液滴通过带相反电荷的聚电解质在水中的液-液相分离形成。 在化学“燃料”的存在下，这些酶催化改变局部条件的反应（例如，pH），从而提高液滴稳定性。重要的是，自组装和新陈代谢的过程是相互依赖的，并允许工程积极和消极的反馈回路。 自组装通过在小体积内浓缩酶来增强代谢活性，从而增加代谢产物的局部浓度。 反应诱导的浓度变化用于增强或抑制自组装，这取决于材料和反应的选择。 基于设计的基于增压过氧化氢酶的代谢材料，该材料响应于由H2 O2燃料分解驱动的pH变化-该提议的工作旨在（1）设计富含增压酶的凝聚层液滴的pH依赖性相行为;（2）量化代谢活性及其在改变液滴环境中的影响;以及（3）利用正负反馈耦合新陈代谢和自组装，以实现动态功能。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。

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.