Molecular Design of Nonfouling and Smart Materials

非特异性蛋白质吸附的表面阻力是目前人们非常感兴趣的研究课题，对生物传感器、植入型生物材料和药物载体的性能至关重要。尽管在蛋白质吸附方面进行了广泛的研究，但仍然缺乏对无污染机理的纳米和分子水平的了解。这项工作中的实验和模拟相结合的研究将针对这一重要问题。智力优势：从PI小组最近完成的模拟和实验研究中，似乎低聚(乙二醇)(OEG)自组装单分子膜(SAM)的无污垢性质与OEG链的水化/柔性之间存在关联。此外，PI的研究小组首次证明，用磷脂酰胆碱(PC)或寡聚(PC)终止的SAM强烈抵抗非特异性蛋白质吸附。亲水性和中性的OEG基团通过氢键形成水化层，而两性离子基团(如PC)通过静电作用形成水化层。两性离子能够结合大量的水分子，因此是潜在的无污染材料的优秀候选者。为了在分子水平上全面而坚实地理解无污染机理，OEG和PCSAM是两个很好的模型体系，因为它们控制良好，并且通过不同的机制与水相互作用。因此，这项工作主要集中在：(A)利用分子模拟技术研究蛋白质与OEG(或PC)自组装膜相互作用的结合水分子的结构和动力学行为、力-距离曲线和自由能变化，(B)从红外可见和频(SFG)探测OEG(或PC)链周围的结合水分子的结构，并利用等温滴定量热法(ITC)和表面等离子体共振(SPR)传感器确定蛋白质吸附的热能、自由能和熵变化，以及(C)研究SMART、无污染和生物相容的离子羧基甜菜碱材料的独特性质及其对离子强度和离子强度变化的响应性更广泛的影响：这项与纳米相关的工作的成功将在分子水平上促进我们对无污染机理的基本理解，为评估无污染材料提供新的标准，并有助于设计新的智能、无污染和生物兼容的材料。它将对各种应用产生重大影响，包括生物传感器、生物材料、组织工程、药物输送、生物分离和海洋涂料。虽然无污染表面对这些技术至关重要，但对无污染机理的基本理解是发现新的防污染材料和涂层的驱动力。研究生和本科生将参与这个项目，特别是那些来自代表性不足群体的学生。本科生研究人员将通过在当地研究中心建立的良好外展计划招募，国际和平研究所一直积极参与其中。PI将开发一门关于生物分子界面的新课程，在拟议的工作中演示的分子产品设计的新概念将是该课程的主旨。此外，这些知识将通过其他课程传播，如纳米技术前沿和材料计算模拟与建模“。

Project AbstractSurface resistance to nonspecific protein adsorption is currently a subject of great interest and is critical to the performance of biosensors, implanted biomaterials, and drug carriers. Despite extensive research in protein adsorption, there is still a lack of a nano-and molecular-level understanding of the nonfouling mechanism. Combined experimental and simulation studies in this work will target this important problem.Intellectual Merit: From recent simulation and experimental studies completed by the PI's group, it appears that there is a correlation between the nonfouling properties of oligo (ethylene glycol) (OEG) self-assembled monolayers (SAMs) and the hydration/flexibility of OEG chains. Furthermore, the PI's group demonstrated for the first time that SAMs terminated with phosphorylcholine (PC) or oligo (PC) groups strongly resist nonspecific protein adsorption. While hydrophilic and neutral OEG groups form a hydration layer via hydrogen bonds, zwitterionic groups (e.g., PC) form a hydration layer via electrostatic interactions. Zwitterions are capable of binding significant amounts of water molecules and therefore are potentially excellent candidates for nonfouling materials. In order to provide a complete and solid understanding of the nonfouling mechanism at the molecular level, OEG and PC SAMs are two excellent model systems since they are well-controlled and interact with water via different mechanisms. Thus, this work focuses on (a) study the structural and dynamic behavior of bound water molecules, force-versus-distance curves, and free energy changes for protein interactions with OEG (or PC) SAMs using molecular simulations techniques, (b) probe the structure of bound water molecules around OEG (or PC) chains from infrared-visible sum frequency generation (SFG) and to determine the enthalpy, free energy, and entropy changes for protein adsorption from isothermal titration calorimetry (ITC) and surface Plasmon resonance (SPR) sensor, and (c) investigate the unique properties of smart, nonfouling, and biocompatible zwitterionic carboxybetaine materials and their responsiveness to changes in ionic strength, pH, and temperature.Broader Impact: The success of this nano-related work will advance our fundamental understanding of the nonfouling mechanism at the molecular level, provide new criteria for evaluating nonfouling materials, and assist the design of new smart, nonfouling, and biocompatible materials. It will have significant impact on various applications, including biosensors, biomaterials, tissue engineering, drug delivery, bioseparation, and marine coatings. While nonfouling surfaces are critical for these technologies, a fundamental understanding of the nonfouling mechanism is a driving force for discoveries of new antifouling materials and coatings. Graduate and undergraduate students will be involved in this project, particularly those from underrepresented groups. Undergraduate researchers will be recruited through well-established outreach programs at local research centers, in which the PI has been actively involved. The PI will develop a new course on Biomolecular Interfaces The new concept of molecular product design as demonstrated in the proposed work will be the main theme of the course. In addition, the knowledge will be disseminated through other courses, such as Frontiers in Nanotechnology and Computational Simulation and Modeling of Materials".