CAREER: Controlling Responsive Biointerfaces by Understanding Elastin Self-Assembled Monolayers

第1部分：非技术总结下一代健康监测和治疗设备的开发需要具有设计具有可预测特性的生物材料界面的能力，以及有效的劳动力来进行发现和推动技术进步。该项目将通过以下方式满足这些需求：1)发展对基于多肽的自组装单层的基本了解，并设计这些界面以具有所需的生物材料特性；2)帮助培养一支拥有生物材料专业知识的多样化劳动力队伍。在该项目中获得的多肽自组装单分子膜的基础知识可以帮助加快用于监测和治疗非传染性疾病的植入性技术的开发，目前非传染性疾病导致全球每年60%以上的死亡和数万亿美元的经济损失。具体地说，该项目将影响药物输送、传感器和捕获-释放应用领域。此外，正在开发一项创新教育计划，以肽为平台，提高高中生、本科生和研究生在工程和设计相关领域的自我效能感，并积极影响大学层面的社会责任态度。自我效能感是一个与学业成绩、坚持性和对学术工作的投入呈正相关的指标。研究生和本科生将通过亲身实践的多肽工程项目学习与行业相关的项目规划技能，然后在独特的服务学习体验中，带领高中生参与相关项目。这项努力是与当地一所高中合作的，那里90%以上的学生来自代表人数较少的少数群体。第2部分：技术总结本项目的主要目标是：1)开发预测多肽自组装单层性质的模型；2)在不同的高中、本科生和研究生群体中提高执行工程任务的自我效能。该研究计划将侧重于对控制刺激反应行为的多肽自组装单层转变温度的基本了解；控制底物访问的有效表面覆盖率；以及控制这些生物材料属性的自组装单层动力学组装。弹性蛋白衍生的序列将被研究，因为弹性蛋白已知具有刺激反应特性，并已被提议用于广泛的生物材料应用。目前，还没有确定的模型来预测弹性蛋白自组装的单层响应行为、有效的表面覆盖率或动态组装。该项目将通过结合使用多肽设计和技术，如具有耗散监测的石英晶体微天平、循环伏安法和时间分辨衰减全反射表面增强红外吸收光谱，来填补科学认识上的这些空白。该研究计划将与新的互动服务学习计划相结合，这些计划将吸引高中、本科和研究生水平的学生参与。一个独特的本科生/研究生水平的项目规划学习模块将被创新，以鼓励学生利用他们的多肽工程知识为东克利夫兰女高中生传授有价值的研究和工程技能的外展项目创建教学内容。学生的自我效能感将使用有效的调查工具在所有级别进行衡量，以评估教育计划的成功。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。

PART 1: NON-TECHNICAL SUMMARYThe development of next-generation health monitoring and treatment devices requires an ability to design biomaterial interfaces with predictable properties, and an effective workforce to make discoveries and propel technological advances. This project will address these needs by 1) developing a fundamental understanding of peptide-based self-assembled monolayers and designing these interfaces to have desired biomaterial properties; and 2) helping to create a diverse workforce with expertise in biomaterials. The fundamental knowledge in peptide self-assembled monolayers gained in this project can help speed the development of implantable technologies for monitoring and treating non-communicable diseases, which currently cause more than 60% of annual worldwide deaths and trillions of dollars in economic losses. Specifically, this project will impact the fields of drug delivery, sensors, and capture-release applications. In addition, an innovative education program is being developed which uses peptides as a platform to increase high school, undergraduate, and graduate students’ self-efficacy in areas related to engineering and design, and positively impact attitudes toward social responsibility at the university level. Self-efficacy is a metric positively related to academic achievement, persistence, and engagement in academic work. Graduate and undergraduate students will learn industry-relevant project planning skills through a hands-on peptide engineering project and then, in a unique service learning experience, lead high school students in related projects. This effort is in partnership with a local high school where over 90% of the students are from underrepresented minority groups. PART 2: TECHNICAL SUMMARYThe main objectives of this project are to 1) develop models that predict the properties of peptide self-assembled monolayers; and 2) increase self-efficacy in performing engineering tasks across a diverse group of high-school, undergraduate and graduate students. The research program will focus on fundamental understanding of peptide self-assembled monolayer transition temperature, which controls stimuli-responsive behavior; effective surface coverage, which controls access to the substrate; and self-assembled monolayer kinetic assembly, which controls these biomaterial properties. Elastin-derived sequences will be studied because elastin is known to have stimuli-responsive properties and has been proposed for a broad range of biomaterials applications. Currently, there are no established models to predict elastin self-assembled monolayer responsive behavior, effective surface coverage, or kinetic assembly. This project will fill these gaps in scientific understanding by using a combination of peptide design and techniques such as quartz crystal microbalance with dissipation monitoring, cyclic voltammetry, and time-resolved attenuated total reflection surface-enhanced infrared absorption spectroscopy. The research program will be coupled with new interactive service learning initiatives that will engage students at the high school, undergraduate, and graduate levels. A unique undergraduate-/graduate-level project planning learning module will be innovated to encourage students to use their peptide engineering knowledge to create pedagogical content for an outreach program with East Cleveland female high school students to teach valuable research and engineering skills. Student self-efficacy will be measured at all levels using validated survey instruments to assess the success of the education programs.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.