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

现代社会面临的一项挑战是为非传染性疾病开发有效的健康监测和治疗设备，非传染性疾病造成的死亡人数占全球每年死亡人数的60%以上。为了应对这一挑战，需要将固体材料与生物系统相结合，其中必须设计界面以避免生物污染，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层，这是一类由分子自发组装而成的纳米结构材料，可以形成一个分子厚的有组织层。目前，常见的防污自组装单层膜存在生物积累、不期望的免疫反应和有限的可调性等缺点。本项目重点研究工程肽作为有前途的自组装材料的新分子框架，因为它们1)易于调节，因此具有多功能的能力，2)具有可控、有序的二级结构，3)自组装成不同的纳米结构，4)具有生物相容性。该项目的目标是对肽的自组装、结构和防污机制提供基本的见解，并建立氨基酸取代进入工程肽框架的设计规则。这一贡献是重要的，因为在这个项目中获得的设计规则将允许基于肽的自组装单层被调整为具有广泛领域的各种功能，并推进可植入的纳米生物技术和其他与生物介质接口的技术。该提案通过扩大外展项目支持教育和多样性，鼓励代表性不足的高中生参加暑期研究项目。此外，将创新一个独特的研究生水平学习模块，以支持国家科学基金会提高研究生就业准备的优先事项。本项目的总体目标是基于对组装、结构和防污的基本理解，开发氨基酸取代成肽自组装单层框架的设计规则。该提案特别关注于聚脯氨酸肽框架，因为它具有3倍对称结构，防污特性，并且具有客体残基替代的潜力。因此，本项目旨在1)了解聚脯氨酸自组装单层的排序和组装机制，2)建立基于聚脯氨酸客体残基框架的设计规则，3)发现基于聚脯氨酸的自组装单层防污机制。目前，对于如何在不影响自组装单层性质或防污的情况下改变肽序列，还没有明确的策略。此外，肽自组装单层的顺序通常没有被表征，组装和防污的动力学和热力学也没有被表征。因此，迫切需要一种基于多肽的框架，这种框架具有可预测和易于理解的自组装、污垢和材料性质。该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肽自组装单层系统，从而解决这一需求。该技术的预期应用领域包括治疗用纳米粒子、纳米游泳器、可植入燃料电池/传感器的纳米结构电极以及催化。因此，本提案通过实现多功能防污表面，解决了实现植入式监测和治疗设备广泛使用的主要挑战。该提案还将通过推广和教育项目对社会产生重大影响。具体来说，首席研究员为女高中生创建了一个新的研究体验项目，旨在鼓励参与者考虑科学和工程职业。首席研究员目前正在与当地一所拥有91%少数族裔学生的高中合作，并计划大幅扩大该项目。此外，研究生将通过创新，动手，项目规划模块学习行业相关技能。该模块的动机是帮助学生在私营部门充分利用他们的技术技能，42%的科学和工程博士学位获得者在私营部门工作。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。

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.