Design and characterization of biofilm-inspired amyloid biomaterials.

生物膜启发的淀粉样蛋白生物材料的设计和表征。

• 批准号: 2208349
• 负责人: Vijay Rangachari
• 金额: $ 53.67万
• 依托单位: University of Southern Mississippi
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-01 至 2025-07-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2208349&HistoricalAwards=false
• 关键词: Design; characterization; biofilm; inspired; amyloid

This project is jointly funded by the Biomaterials program and the Established Program to Stimulate Competitive Research (EPSCoR)BMAT: Design and characterization of biofilm-inspired amyloid biomaterials.Non-technical abstractNature produces materials with extraordinary properties, be it high strength spiderweb made of the protein silk fibroin or robust protective coat of a biofilm by fibers of the bacterial protein Curli. One of the strongest and most stable biological materials is the ‘amyloid’, which is formed from the self-association of proteins that produces densely packed, orderly protein molecules with high stability and robust material properties. The unique self-assembly processes, mechanical robustness, thermal and biocompatibility of amyloid proteins provide a rich platform for potential exploitation of bio-inspired synthetic amyloid materials for various applications. However, the relationship between protein amino acid sequence and material properties of amyloid fibers is lacking. This project brings together an interdisciplinary team with expertise in molecular biophysics, synthetic chemistry, and materials science to establish the relationships between structure, function, processing, and properties in a series of de novo peptides designed to mimic specific sequences of Curli amyloids. The fundamental understanding of structure-property relationships in the novel amyloid materials generated will serve as a platform for the development of functional biomaterials for biotechnological and pharmacological applications. As a part of this project, graduate and undergraduate students will be engaged in the research and cross-trained in faculty laboratories. Outreach efforts will be designed to engage the full diversity of Mississippi’s population, which is among the poorest in the nation and represents the highest African American population as a percentage of total population. Technical abstractAlthough amyloids are linked to many pathologies, it is becoming abundantly clear that they also play functional roles required for cellular processes in bacteria, fungi, insects, invertebrates, and humans. In bacteria, the protein CsgA Curli forms amyloid fibers that are important components of extracellular biofilms, coatings under which bacterial colonies thrive evading various environmental insults. Curli amyloids are structurally conserved cross-β-sheet structures that accommodate tightly packed interactions to provide robust material characteristics for biofilms. We hypothesize that based on the CsgA sequence as a template, ¬¬effective variant amyloid antimicrobial materials can be designed through sequence-morphology-bioactivity correlations. The proposed research will test this hypothesis and will address the question of how type and positional biases of amino acid in the sequence correlate to biochemical, morphology, and mechanical properties of the aggregates. These will be accomplished with two specific aims: The first aim will focus on the rational design, synthesis and biophysical characterization of peptides and peptide mimics along with their cellular and anti-microbial activities from cues derived from Curli. The second aim will focus on material properties such as morphology and nanomechanical stability, porosity, and ability to form hydrogels. Together, the proposed iterative approach will lay a foundation for designing amyloid materials inspired by Curli, based on sequence, structure, morphology, and microbial activity. This will enhance our current understanding of de novo amyloids in fundamental cellular processes and facilitate the development of biomaterials for pharmaceutical and biotechnology applications.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.

该项目由生物材料计划和刺激竞争力研究的既定计划（EPSCoR）BMAT共同资助：生物膜启发的淀粉样蛋白生物材料的设计和表征。非技术摘要自然产生具有非凡特性的材料，无论是由蛋白质丝素蛋白制成的高强度蜘蛛网还是由细菌蛋白质Curli纤维制成的生物膜的坚固保护涂层。最强、最稳定的生物材料之一是“淀粉样蛋白”，它是由蛋白质自结合形成的，可产生致密、有序的蛋白质分子，具有高稳定性和强大的材料特性。淀粉样蛋白独特的自组装过程、机械鲁棒性、热和生物相容性为潜在开发用于各种应用的生物启发合成淀粉样蛋白材料提供了丰富的平台。然而，蛋白质氨基酸序列与淀粉样纤维的材料性质之间的关系缺乏。该项目汇集了一个具有分子生物物理学，合成化学和材料科学专业知识的跨学科团队，以建立一系列从头肽的结构，功能，加工和特性之间的关系，旨在模拟Curli淀粉样蛋白的特定序列。对所产生的新型淀粉样蛋白材料的结构-性质关系的基本理解将作为开发用于生物技术和药理学应用的功能性生物材料的平台。作为该项目的一部分，研究生和本科生将参与研究，并在教师实验室进行交叉培训。外联工作的目的是使密西西比人口的多样性充分参与，密西西比是全国最贫穷的地区之一，非洲裔美国人在总人口中所占比例最高。尽管淀粉样蛋白与许多病理学有关，但越来越清楚的是，它们也在细菌、真菌、昆虫、无脊椎动物和人类的细胞过程中发挥功能性作用。在细菌中，蛋白CsgA Curli形成淀粉样纤维，其是细胞外生物膜的重要组成部分，细菌菌落在其下茁壮成长以逃避各种环境侵害。卷曲淀粉样蛋白是结构上保守的交叉β-折叠结构，其适应紧密堆积的相互作用，为生物膜提供稳健的材料特性。我们假设基于CsgA序列作为模板，可以通过序列-形态-生物活性相关性设计有效的变体淀粉样蛋白抗微生物材料。拟议的研究将测试这一假设，并将解决序列中氨基酸的类型和位置偏差如何与聚集体的生物化学，形态学和机械特性相关的问题。 这些将完成两个具体的目标：第一个目标将集中在合理的设计，合成和肽和肽模拟物的生物物理特性沿着与他们的细胞和抗微生物活性的线索来自Curli。第二个目标将集中在材料特性，如形态和纳米机械稳定性，孔隙率和形成水凝胶的能力。总之，所提出的迭代方法将为基于序列、结构、形态和微生物活性设计受Curli启发的淀粉样蛋白材料奠定基础。这将增强我们目前对基本细胞过程中的从头淀粉样蛋白的理解，并促进制药和生物技术应用的生物材料的开发。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知识价值和更广泛的影响审查标准进行评估来支持。