Coacervate formation in amino acid functionalized polypeptides

凝聚是一种过程，通过在称为聚电解质的长大分子上的正负基团之间的吸引静电力，使它们聚集并从与水作为聚电解质凝聚体的混合物中分离出来。这些凝集物与细胞细胞器有相似之处，细胞细胞器含有固有的无序蛋白质，没有被包裹在膜中，因此它们被称为无膜细胞器。蛋白质凝聚体与许多重要的生物过程有关，也是海洋生物生产的防潮粘合剂的关键成分，这些粘合剂在医学上用作外科密封剂。利用凝聚来制造可用作药物载体、细胞支架或工程应用的材料也引起了相当大的兴趣。加州大学洛杉矶分校的蒂莫西·戴明教授的研究小组正在开发一种新的凝聚体形成多肽，这种多肽是对天然蛋白质的合成模拟，其性质可以根据特定用途进行快速调整。凝聚形成多肽的研究可用于更好地模拟和理解无序蛋白质的物理行为，以及制备生物粘附剂和仿生人工细胞器。该项目还有助于开发科学、技术、工程和数学方面的人力资源。具体地说，PI为加州大学洛杉矶分校国际制药工程学会学生分会的成员提供指导。他还培训生物工程本科生，这些本科生在工程实验室从事跨学科项目，并有医学院的合作者。参加加州大学洛杉矶分校工程学院工程科学队外展计划的研究型高中生的PI导师。这个暑期研究项目旨在让来自洛杉矶地区的当地少数族裔学生在加州大学洛杉矶分校的研究实验室学习并为工程职业做准备。该项目专注于(I)多肽的设计、制备和表征，这些多肽的侧链使其很好地模拟凝聚形成蛋白，并允许它们的性质进行调整或切换，以及(Ii)包含不同亲水性和α-螺旋凝聚形成结构域的嵌段共聚多肽的设计、制备和表征，并能对环境刺激(如温度和pH)做出响应。研究小组致力于确定控制分子对温度和pH的反应的分子参数。这项研究的一个开创性方面是，嵌段共聚肽可以有多个单独的链段，每个链段对温度、离子或氧化还原变化敏感；因此，刺激的组合可以在组装中产生不同的反应。所建议的材料旨在形成水凝胶。这种材料对环境刺激的反应能力赋予了它们在生物学上的潜在效用。这一奖项反映了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。

Coacervation is a process by which attractive electrostatic forces between positive and negative groups on long macromolecules called polyelectrolytes cause their aggregation and separation out of a mixture with water as a polyelectrolyte coacervate. These coacervates have similarities to cellular organelles that contain intrinsically disordered proteins and are not encapsulated in a membrane, hence their being named "membraneless organelles". Protein coacervates have been linked to many important biological processes and are also known to be key components of moisture-resistant adhesives produced by marine organisms, which have applications in medicine as surgical sealants. There is also considerable interest in use of coacervation to create materials that can be used as drug carriers, cell scaffolds, or for engineering applications. The research group of Professor Timothy Deming at University of California Los Angeles is developing a new class of coacervate-forming polypeptides, which are synthetic mimics of natural proteins and whose properties can be rapidly tuned for specific uses. The study of coacervate-forming polypeptides can be used in the efforts to better mimic and understand the physical behavior of disordered proteins and to prepare bioadhesives and biologically-inspired artificial organelles. This project is also contributing to the development of human resources in science, technology, engineering and mathematics. Specifically, the PI provides mentorship to the members of the International Society for Pharmaceutical Engineering Student Chapter at UCLA. He also trains bioengineering undergraduate students who work on interdisciplinary projects in an engineering lab and who have a medical school collaborator. The PI mentors in research high school students who participate in the Engineering Science Corps Outreach Program of the UCLA School of Engineering. This summer research program is designed to bring local underrepresented minority students from the LA area in research labs at UCLA where they learn about, and prepare for, careers in engineering.This project is focused on the (i) design, preparation and characterization of polypeptides whose sidechains makes them good mimics of coacervate-forming proteins and allows their properties to be tuned or switched, and on the (ii) design, preparation and characterization of block co-polypeptides that contain distinct hydrophilic and alpha-helical coacervate-forming domains and can form hydrogels responsive to environmental stimuli, such as the temperature and pH. The research team works to identify the molecular parameters that control the response of the molecules to temperature and pH. A pioneering aspect of this research is that the block copolypeptides can have multiple individual chain segments, each sensitive to temperature, ion, or redox changes; hence combinations of stimuli can generate different responses in the assemblies. The proposed materials are designed to form hydrogels. The material's ability to respond to environmental stimuli confers them potential utility in biology.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.