Collaborative Research: DMREF: De Novo Proteins as Junctions in Polymer Networks

非技术性描述：大自然使用蛋白质来创造从蜘蛛丝到人体组织的生物材料。利用蛋白质的合成材料具有作为生物可降解塑料和复合材料（蛋白质-聚合物网络）的潜力。关键是要了解蛋白质的设计参数，决定所需的材料在蛋白质-聚合物网络的结果。除了蛋白质结构之外，聚合物网络的拓扑结构在这些材料的机械响应中起着重要作用。虽然这些材料的机械性能可以通过实验确定，但计算模拟可以为蛋白质在网络结构内展开时的机械响应提供关键的见解。我们的提案的变革性科学方面是（i）从头设计的蛋白质及其各自的蛋白质-聚合物网络的合成和计算模拟，以及（ii）微观尺度上聚合物-蛋白质网络的机械表征技术，这将加速蛋白质作为生物混合塑料和工程生物塑料聚合物网络中的接头的发现和部署。此外，3D打印将实现零件的分布式制造，以及建筑师、工程师和其他用户可以创建的定制设计。该项目通过减少碳足迹（降低运输成本和绿色生产）和化学循环（蛋白质基材料的化学回收）来满足国家对更可持续建筑环境的先进制造方法的需求。该项目还解决了国家需要发展下一代高技能和多样化的未来劳动力。技术描述：该提案的中心目标是阐明从头设计的蛋白质作为蛋白质-聚合物网络中的机械响应接头的设计原则。计算从头蛋白质设计和材料科学的融合提供了一个独特的机会，创造基于蛋白质的热固性材料，是上级传统的合成材料。可以优化设计的蛋白质的结构和组成，以控制蛋白质的可加工性（通过增材制造）和材料的整体机械性能。特别是，蛋白质可以作为机械载体，响应外部机械力释放其储存的长度。决定储存长度的因素包括伸展蛋白质的标称长度、每个蛋白质接头的链数和机械展开蛋白质所需的力。蛋白质-聚合物网络的拓扑结构在这些材料的机械响应中也起着重要作用。虽然这些材料的机械性能可以通过实验确定，但计算模拟可以为蛋白质在网络中的展开和重折叠提供关键的见解，并最终加速发现先进材料的蛋白质。这个DMREF项目将（i）开发从头设计的蛋白质，这些蛋白质可以很容易地转化为聚合物网络内的连接，（ii）研究从头设计的蛋白质作为在网络内展开的机械响应连接，以及（iii）展示智能蛋白质的增材制造-通过蛋白质解折叠和重折叠重塑的聚合物网络。该奖项反映了NSF的法定使命，并被认为值得支持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。

Non-technical Description: Nature uses proteins to create biomaterials that range from spider silk to human tissue. Synthetic materials that utilize proteins have potential as biodegradable plastics and composites (protein-polymer networks). It is critical to understand the protein design parameters that determine the desired material outcomes in protein-polymer networks. In addition to protein structure, the topology of the polymer network serves an important role in the mechanical response of these materials. While the mechanical properties of these materials can be experimentally determined, computational simulations can provide critical insights into the mechanical response of proteins as they unfold within a network structure. The transformative scientific aspects of our proposal are (i) the synthesis and computational simulations of de novo designed proteins and their respective protein-polymer networks and (ii) techniques for mechanical characterization of polymer-protein networks on the microscale that will accelerate the discovery and deployment of proteins as junctions in polymer networks for biohybrid plastics and engineering bioplastics. Additionally, 3D printing will enable the distributed manufacturing of parts, as well as custom designs that can be created by architects, engineers, and other users. This project addresses the national need for advanced manufacturing methods that are more sustainable built environments via reduced carbon footprint (reduced transport costs and greener production) and chemical circularity (chemical recycling of protein-based materials). This project also addresses the national need to develop the next generation of a highly skilled and diverse future workforce.Technical Description: The central objective of this proposal is to elucidate the design principles for de novo designed proteins as mechano-responsive junctions in protein-polymer networks. The convergence of computational de novo protein design and materials science presents a unique opportunity to create protein-based thermosets that are superior to conventional synthetic materials. The structure and composition of designed proteins can be optimized to control the processability of the proteins (via additive manufacturing) and the bulk mechanical properties of the materials. In particular, proteins can serve as mechanophores that respond to extrinsic mechanical forces to release their stored length. The factors that determine the stored length include the nominal length of the outstretched protein, the number of strands per protein junction and the force required to mechanically unfold the protein. The topology of the protein-polymer network also serves an important role in the mechanical response of these materials. While the mechanical properties of these materials can be experimentally determined, computational simulations can provide critical insights into proteins unfolding and refolding in a network and ultimately accelerate the discovery of proteins for advanced materials. This DMREF project will (i) develop de novo designed proteins that can be readily transformed into junctions within polymer networks, (ii) investigate de novo designed proteins as mechano-responsive junctions that unfold within networks, and (iii) demonstrate the additive manufacturing of intelligent protein-polymer networks that remodel via protein unfolding and refolding.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.