CAREER: Post-translationally Lipidated Biopolymers As Multiphasic All-Aqueous Emulsions

职业：翻译后脂质化生物聚合物作为多相全水乳液

• 批准号: 2146168
• 负责人: Davoud Mozhdehi
• 金额: $ 58.28万
• 依托单位: Syracuse University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-06-01 至 2027-05-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2146168&HistoricalAwards=false
• 关键词: CAREER; Post; translationally; Lipidated; Biopolymers

This award is funded in whole or in part under the American Rescue Plan Act of 2021 (Public Law 117-2).PART 1: NON-TECHNICAL SUMMARY Emulsions are suspensions of two immiscible liquids, which are ubiquitously utilized across many industries for diverse applications. The research goal of this CAREER project is to synthesize biomaterial-based water-in-water emulsions using a process inspired by natural cell biology. Cells create such emulsions by leveraging phase separation of their intracellular proteins and have developed capabilities to tailor the properties of these emulsions by modifying the phase separating proteins using a diverse palette of chemical reactions. Our understanding of how these modifications stabilize or tailor the water-water interfaces remains incomplete, which increases our reliance on traditional oil-based emulsions. To address this challenge and advance the field of biomaterial design, this research uses a combination of genetic and chemical manipulation to synthesize and study phase-separating proteins with customizable modification patterns. The size and stability of resulting emulsions will be characterized and will be correlated to the modification patterns. The knowledge gained from these studies will be used to create water-in-water emulsions that can be precisely controlled to have user-defined characteristics. Due to their biocompatibility, such new water-in-water emulsions have great potential to replace traditional oil-based emulsions in food processing, cosmetics, biosensing, and delivery of pharmaceuticals. This project will provide the materials science community with innovative and easy-to-use platforms for scalable synthesis of biomaterials and help accelerate the ability to manufacture the next generation of structurally complex, functionally tunable biomaterials for multiple industrial and healthcare applications. This will strengthen the U.S.'s leadership in the global bioeconomy. Educational activities supported through this project will train the next generation of scientists and engineers in bio-enabled technologies. A major educational activity is the student creation of biodegradable and eco-friendly materials for fabric and textile applications. Applications of this work can address the highly polluting and environmentally damaging current practices in textile manufacturing. This educational activity will be used in outreach to attract and engage high school students to this merger of science and design. In addition, this project will inform the redesign of an undergraduate and graduate laboratory course that will involve students in real-world discovery and will train students in the regulatory framework used in the biotechnology industry. PART 2: TECHNICAL SUMMARY This CAREER project will exploit the bio-enabled process of post-translational modification (PTM) to advance the goal of rationally designing hybrid biomaterials with functionality that exceeds the capabilities of natural biopolymers. The study will decrypt the material-design principles of phase-separating lipidated proteins (PLPs) to create water-in-water emulsions with user-defined formation, fluid properties, and internal structure. The study will investigate the overarching hypothesis that the physicochemical interplay between the protein, lipid, and lipidation site domains regulates the strength and half-life of adhesive and cohesive interactions that control the formation, viscoelasticity, and hierarchical organization of PLP condensates. Three research objectives will elucidate the molecular and thermodynamically grounded descriptions of how lipidation PTM alters the interfacial and rheological characteristics of model protein condensates: (1) correlate the thermodynamic stability of PLP emulsions to the physicochemistry of lipid and phase-separating proteins, (2) ascertain the effect of lipidation site sequence on the dynamics of cohesive interactions and colloidal properties of biphasic PLP emulsions, and (3) determine the molecular factors that regulate the strength of adhesive microscopic interactions and macroscopic miscibility of multiphasic PLP emulsions. Methods to achieve these objectives include bio-/semi-synthesis of PLPs to create libraries with systematically varied lipid, protein, and lipidation sites; determination of phase boundaries using light scattering techniques; and characterization of dynamic material properties of PLP droplets using microscopy and phase-separated states using rheology. Multidimensional nuclear magnetic resonance techniques will be used to investigate the defining structural and dynamic elements of PLPs to enable the rational design of the next generation of condensates with tailorable structural and material properties. The education plan integrates these research efforts into a multitiered approach to (1) increase the public's awareness of bio-enabled materials and technologies as solutions to societally relevant problems, (2) recruit underrepresented minorities from nontraditional backgrounds to biomaterials research, and (3) enhance biomaterials education at the undergraduate and graduate levels.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.

该奖项全部或部分由《2021年美国救援计划法案》（公法117-2）资助。乳剂是两种不混溶液体的悬浮液，在许多行业的不同应用中无处不在。CAREER项目的研究目标是利用受自然细胞生物学启发的方法合成基于生物材料的水包水乳剂。细胞通过利用细胞内蛋白质的相分离来制造这种乳剂，并且已经开发出通过使用不同的化学反应调色板修改相分离蛋白质来定制这些乳剂特性的能力。我们对这些修饰如何稳定或调整水-水界面的理解仍然不完整，这增加了我们对传统油基乳液的依赖。为了应对这一挑战并推动生物材料设计领域的发展，本研究采用遗传和化学操作相结合的方法来合成和研究具有可定制修饰模式的相分离蛋白质。所得到的乳剂的大小和稳定性将被表征，并将与改性模式相关联。从这些研究中获得的知识将用于创建水包水乳液，可以精确控制，具有用户定义的特性。由于其生物相容性，这种新型水包水乳剂在食品加工、化妆品、生物传感和药物输送等领域具有取代传统油基乳剂的巨大潜力。该项目将为材料科学界提供创新和易于使用的平台，用于可扩展的生物材料合成，并有助于加速制造用于多种工业和医疗保健应用的下一代结构复杂，功能可调的生物材料的能力。这将使美国更加强大美国在全球生物经济中的领导地位。该项目支持的教育活动将培训下一代生物技术方面的科学家和工程师。一项主要的教育活动是学生为织物和纺织应用创造可生物降解和环保的材料。这项工作的应用可以解决目前纺织制造业中高污染和环境破坏的做法。这项教育活动将用于推广，以吸引和吸引高中生参与这种科学与设计的融合。此外，该项目将为本科生和研究生实验课程的重新设计提供信息，这些课程将让学生参与现实世界的发现，并将培训学生使用生物技术行业的监管框架。本职业项目将利用翻译后修饰（PTM）的生物激活过程来推进合理设计具有超过天然生物聚合物功能的混合生物材料的目标。该研究将解密相分离脂化蛋白（PLPs）的材料设计原则，以创建具有用户定义的形成、流体性质和内部结构的水包水乳剂。该研究将调查一个总体假设，即蛋白质、脂质和脂化位点区域之间的物理化学相互作用调节着粘附和内聚相互作用的强度和半衰期，这些相互作用控制着PLP凝聚物的形成、粘弹性和分层组织。三个研究目标将阐明脂化PTM如何改变模型蛋白质凝聚物的界面和流变特性的分子和热力学基础描述：(1)将PLP乳剂的热力学稳定性与脂质和分相蛋白的物理化学性质联系起来；(2)确定脂化位点序列对双相PLP乳剂的内聚相互作用动力学和胶体性质的影响；(3)确定调节多相PLP乳剂微观相互作用强度和宏观混相的分子因素。实现这些目标的方法包括生物/半合成PLPs，以创建具有系统变化的脂质、蛋白质和脂化位点的文库；利用光散射技术确定相界；以及用显微镜和流变学方法表征PLP液滴的动态材料特性。多维核磁共振技术将用于研究plp的定义结构和动态元素，从而能够合理设计具有定制结构和材料特性的下一代凝析油。该教育计划将这些研究工作整合到一个多层次的方法中，以(1)提高公众对生物材料和技术作为社会相关问题解决方案的认识，(2)从非传统背景中招募代表性不足的少数民族从事生物材料研究，(3)加强本科和研究生阶段的生物材料教育。该奖项反映了美国国家科学基金会的法定使命，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。