EAGER: Understanding Molecular Control and Phase Behavior of Random Heteropolymer Materials for Selective Transport

非技术综述：在自然界中，膜蛋白是调节分子运输以维持细胞过程的守门人。如果聚合物的分离性能与膜蛋白相似，它们将对环境、能源、分离技术和生命科学产生重大影响。例如，膜在水净化和海水淡化、二氧化碳捕获和分离、化学净化和锂电池应用中的使用率很高。几十年来，人们在改进聚合物化学和自组装以更好地模拟膜蛋白的已知结构方面做出了重大努力，但这些努力导致了膜性能的有限进步。瓶颈是在这些高度复杂和多样化的生物系统中确定关键的设计参数。通过从根本上了解插入到细胞脂质类似物中的聚合链的空间排列并将其与分子运输相关联，该项目旨在为长期存在的问题提供见解：“复制蛋白质运输特性需要对聚合物材料进行何种程度的分子控制？”如果成功，该项目可能会产生生物启发聚合物的新设计规则，改变膜开发的途径，并导致技术相关的膜。拟议的研究是高度跨学科的，并为培训各级学生提供了一个极好的平台。它们还将为聚合物分析提供软件工具以及多个扩展机会。技术摘要：对于膜蛋白，人们普遍认为，明确定义的蛋白质结构是同时实现高通量和选择性的必要条件。几十年来，遵循这一规律设计了各种多孔材料，并探索了用于选择性传输的方法，但成效有限。基于随机杂化聚合物的初步结果，拟议研究的中心假设是，一旦杂化聚合物组成固定，统计单体分布，而不是原子上精确的聚合物结构，是控制所产生的传输特性的关键参数。本项目旨在通过以下方式验证这一假设：(1)开发软件工具来执行随机的杂聚序列的深入分析；(2)表征脂类插入时杂聚物链的构象，以将杂聚物相行为与快速、选择性的质子传输相关联；(3)探索基于杂聚物的嵌段共聚物，用于分析杂聚物链的构象和传输特性，用于未来的膜设计。初步结果表明，在质子运输方面，非结构聚合物链的性能可能与折叠良好的蛋白质类似。计划中的探索性研究将确定这种行为背后的关键设计参数，这可能会影响目前的膜设计方法。这一结果还可能改变对天然生物聚合物结构-功能关系的传统观点，并影响生物启发聚合物的未来发展。基于活性聚合的最新进展，这一结果将很好地适用于生产具有重要技术意义的膜。此外，计划中的研究将：(1)提供研究生和本科生的研究机会，以及通过与加州学院合作，为公众和中学生提供聚合物教育的外展机会；(2)开发用于杂聚分析的新软件工具，并将其公开提供；以及(3)为材料社区提供机制，以克服启动杂聚相关项目的障碍。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

NON-TECHNICAL SUMMARY:In nature, membrane proteins are the gatekeepers that mediate molecular transport to maintain cellular processes. If polymers can be generated with separation performance similar to that of membrane proteins, they could offer very significant impacts on the environment, energy, separation technologies, and life sciences. For example, membranes are in high use for water purification and desalination, carbon dioxide capture and separation, chemical purification, and lithium battery applications. Over decades there have been significant efforts in improving polymer chemistry and self-assembly to better mimic the known structures of membrane proteins, which have led to limited advances in membrane performance. The bottleneck is to identify critical design parameters in these highly complex and diverse biological systems. By fundamentally understanding the spatial arrangement of a polymer chain inserted in a cellular lipid analogue and correlating it with molecular transport, this project aims to provide insights to the long-standing question: "what level of molecular control over polymeric materials is needed to replicate protein transport properties?" If successful, the project may result in new design rules for bio-inspired polymers, change the pathways for membrane development, and lead to technologically relevant membranes. The proposed studies are highly interdisciplinary and afford an excellent platform for training students at all levels. They will also provide software tools for polymer analysis as well as multiple outreach opportunities.TECHNICAL SUMMARY:For membrane proteins the common belief is that well-defined protein structure is requisite to simultaneously achieving high flux and selectivity. For decades, various porous materials have been designed following this rule and explored for selective transport with limited success. Based on preliminary results using random heteropolymers, the central hypothesis for the proposed study is that once the heteropolymer composition is fixed, the statistical monomer distribution, rather than the atomically precise polymer structure, is the key parameter governing the resulting transport properties. This project aims to test this hypothesis by: (1) developing software tools to perform in-depth analysis of random heteropolymer sequence; (2) characterizing heteropolymer chain conformation upon lipid insertion to correlate the heteropolymer phase behavior with rapid, selective proton transport; (3) exploring heteropolymer-based block copolymers for analysis of heteropolymer chain conformation and transport properties for future membrane design. Preliminary results point to the potential that unstructured polymer chains can perform at similar level as well-folded proteins for proton transport. The planned exploratory studies will identify the critical design parameters behind such behavior, which may impact the current approach to designing membranes. The results may also change the traditional view on structure-function relationships in naturally occurring biopolymers and affect future development of bio-inspired polymers. Based on recent advances in living polymerization, the results would be well posed to generate technologically important membranes. Furthermore, the planned studies will: (1) provide graduate and undergraduate research opportunities, as well as outreach opportunities through a joint effort with the California Academy for educating the public and middle school students on polymers; (2) develop new software tools for heteropolymer analysis and make them publicly available; and (3) provide the materials communities with a mechanism to overcome a barrier in starting heteropolymer-related projects.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.