Coacervate formation in amino acid functionalized polypeptides

凝聚是一个过程，通过该过程，称为聚电解质的长大分子上的正电和负电基团之间的静电吸引力导致它们聚集并从与水的混合物中分离出来，形成聚电解质凝聚层。 这些凝聚体与含有内在无序蛋白质的细胞器具有相似性，并且不包封在膜中，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，并且已知是由海洋生物产生的防潮粘合剂的关键组分，其在医学中作为外科密封剂应用。也有相当大的兴趣在使用凝聚产生的材料，可用作药物载体，细胞支架，或用于工程应用。洛杉矶加州大学的蒂莫西德明教授的研究小组正在开发一类新的凝聚体形成多肽，它们是天然蛋白质的合成模拟物，其性质可以快速调整以用于特定用途。凝聚体形成多肽的研究可以用于更好地模拟和理解无序蛋白质的物理行为，并制备生物粘合剂和生物启发的人工细胞器。该项目还有助于科学、技术、工程和数学方面的人力资源开发。 具体而言，PI为加州大学洛杉矶分校国际制药工程学生分会的成员提供指导。 他还培训生物工程本科生，他们在工程实验室从事跨学科项目，并与医学院合作。PI导师在研究高中学生谁参加工程学院的加州大学洛杉矶分校工程学院的工程科学团推广计划。 这个暑期研究项目的目的是把当地代表性不足的少数民族学生从洛杉矶地区在加州大学洛杉矶分校的研究实验室，他们学习，并准备，工程职业生涯。这个项目的重点是（i）设计，制备和表征多肽的侧链使他们很好地模拟凝聚形成蛋白质，并允许他们的性质进行调整或切换，并在（ii）设计，制备和表征含有不同的亲水性和α-螺旋凝聚层形成结构域并可响应环境刺激形成水凝胶的嵌段共多肽，研究小组致力于确定控制分子对温度和pH的响应的分子参数。这项研究的一个开创性方面是嵌段共聚肽可以具有多个单独的链段，每个对温度、离子或氧化还原变化敏感;因此刺激的组合可以在组件中产生不同的响应。所提出的材料被设计成形成水凝胶。这种材料对环境刺激的反应能力赋予了它们在生物学中的潜在用途。该奖项反映了NSF的法定使命，并被认为值得通过使用基金会的智力价值和更广泛的影响审查标准进行评估来支持。

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.