Tuning the Interactions between Biomolecules and Surfaces via a Peptide Self-Assembled Monolayer Framework

通过肽自组装单层框架调节生物分子和表面之间的相互作用

• 批准号: 2026259
• 负责人: Julie Renner
• 金额: $ 29.88万
• 依托单位: Case Western Reserve University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-01 至 2024-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2026259&HistoricalAwards=false
• 关键词: Tuning; Interactions; between; Biomolecules; Surfaces

A modern societal challenge is to develop effective health monitoring and treatment devices for non-communicable diseases, which cause more than 60% of annual worldwide deaths. Meeting this challenge involves integrating solid materials with biological systems where the interfaces must be engineered to avoid biofouling and simultaneously maintain complex functionalities. One way to engineer the interface between solids and biological systems is through self-assembled monolayers, a class of nanostructured materials composed of molecules which assemble spontaneously to make and organized layer that is one molecule thick. Currently, common antifouling self-assembled monolayers have drawbacks such as bioaccumulation, undesired immune responses and limited tunability. This project focuses on engineered peptides as promising new molecular frameworks for self-assembled materials because they 1) are easily tunable and therefore have the capacity to be multi-functional, 2) possess controllable, ordered secondary structures, 3) self-assemble into different nanostructures, and 4) are biocompatible. The goal of this project is to provide fundamental insight into peptide self-assembly, structure and antifouling mechanisms and establish design rules for amino acid substitution into the engineered peptide framework. This contribution is significant because the design rules gained in this project will allow peptide-based self-assembled monolayers to be tuned to have a variety of functionalities for a broad range of fields, and advance implantable nanobiotechnologies and other technologies which interface with biological media. This proposal supports education and diversity through an expanded outreach program which encourages underrepresented high school students to participate in summer research programming. In addition, a unique graduate-level learning module will be innovated which supports the National Science Foundation’s priorities for improving graduate student workforce preparedness. The overall objective of this project is to develop design rules for amino acid substitution into a peptide self-assembled monolayer framework based on a fundamental understanding of assembly, structure, and antifouling. This proposal specifically focuses on a polyproline peptide framework because it features a 3-fold symmetrical structure, antifouling properties, and has the potential for guest residue substitution. Thus, this project aims to 1) understand the ordering and assembly mechanisms of polyproline self-assembled monolayers, 2) establish design rules based on a polyproline-guest residue framework, and 3) discover polyproline-based self-assembled monolayer antifouling mechanisms. Currently, there is no clear strategy for how to make changes to peptide sequences without negatively impacting self-assembled monolayer properties or antifouling. In addition, the ordering of peptide self-assembled monolayers is often not characterized nor are the kinetics and thermodynamics of assembly and antifouling. Therefore, there exists an urgent need for a peptide-based framework that has predictable and well-understood self-assembly, fouling, and material properties. This project will address that need by studying a peptide self-assembled monolayer system featuring guest residues via in situ monitoring and advanced surface characterizations. Anticipated fields where the technology will be used include therapeutic nanoparticles, nanoswimmers, nanostructured electrodes for implantable fuel cells/sensors, and catalysis. Thus, this proposal addresses major challenges to realizing widespread use of implantable monitoring and treatment devices by enabling multifunctional antifouling surfaces. This proposal will also have a high impact on society through outreach and educational programs. Specifically, the principle investigator has created a new research experience program for female high school students designed to encourage participants to consider science and engineering careers. The principle investigator is currently working with a local high school that has 91% minority students, and plans to significantly grow the program. Additionally, graduate students will learn industry-relevant skills through an innovative, hands-on, project planning module. The motivation for the module is to help students best-utilize their technical skills in the private sector, where 42% of doctoral recipients in science and engineering work.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.

现代社会的一个挑战是为非传染性疾病开发有效的健康监测和治疗设备，每年全球60%以上的死亡是由非传染性疾病造成的。应对这一挑战需要将固体材料与生物系统相结合，其中接口必须经过设计，以避免生物污垢，同时保持复杂的功能。设计固体和生物系统之间界面的一种方法是通过自组装单分子层，这是一类纳米结构材料，由分子自发组装而成，并组织成一分子厚的层。目前，常用的防污自组装单分子膜存在生物蓄积、免疫应答不理想和可调性有限等缺点。本项目的重点是工程化多肽作为新的自组装材料的分子骨架，因为它们1)容易调节，因此具有多功能的能力，2)具有可控的、有序的二级结构，3)自组装成不同的纳米结构，以及4)生物相容性。该项目的目标是提供对多肽自组装、结构和防污染机制的基本见解，并建立工程多肽框架中氨基酸替代的设计规则。这一贡献意义重大，因为在该项目中获得的设计规则将允许基于多肽的自组装单分子层进行调整，使其具有广泛领域的各种功能，并推动可植入纳米生物技术和其他与生物介质相互作用的技术。这项提案通过扩大外展计划来支持教育和多样性，该计划鼓励代表人数不足的高中生参加暑期研究计划。此外，还将创新一个独特的研究生水平的学习模块，以支持国家科学基金会改善研究生劳动力准备的优先事项。这个项目的总体目标是在对组装、结构和防污的基本了解的基础上，开发氨基酸取代为多肽自组装单层框架的设计规则。这项建议特别关注多聚脯氨酸多肽框架，因为它具有3重对称结构，具有防污性能，并具有客体残基替代的潜力。因此，本项目的目标是1)了解多聚脯氨酸自组装单分子膜的有序性和组装机理，2)建立基于多脯氨酸-客体残基框架的设计规则，3)发现基于多脯氨酸的自组装单分子膜防污机理。目前，对于如何在不对自组装单分子膜性能或防污染产生负面影响的情况下对肽序列进行改变还没有明确的策略。此外，多肽自组装单分子膜的有序性通常没有被表征，组装和防污染的动力学和热力学也是如此。因此，迫切需要一种基于多肽的框架，该框架具有可预测的和众所周知的自组装、污垢和材料性质。这个项目将通过原位监测和先进的表面表征来研究具有客体残基的多肽自组装单层系统，以满足这一需求。该技术的预期应用领域包括治疗性纳米颗粒、纳米微米、用于植入式燃料电池/传感器的纳米结构电极和催化。因此，这项提议解决了通过实现多功能防污表面来实现植入式监测和治疗设备的广泛使用的主要挑战。这项提案还将通过外展和教育项目对社会产生高度影响。具体地说，首席调查员为女高中生创建了一个新的研究体验计划，旨在鼓励参与者考虑科学和工程职业。这位首席调查员目前正在与当地一所拥有91%少数民族学生的高中合作，并计划大幅扩大该项目。此外，研究生将通过创新的、动手操作的项目规划模块学习与行业相关的技能。该单元的动机是帮助学生在私营部门最好地利用他们的技术技能，42%的科学和工程博士获得者在私营部门工作。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。

项目成果

Self-Assembly and Rearrangement of a Polyproline II Helix Peptide on Gold

• DOI: 10.1021/acs.langmuir.0c03583
• 发表时间: 2021-05-11
• 期刊: LANGMUIR
• 影响因子: 3.9
• 作者: Hostert, Jacob D.;Loney, Charles N.;Renner, Julie N.
• 通讯作者: Renner, Julie N.