Molecular Design of Nonfouling and Smart Materials

表面对非特异性蛋白质吸附的抵抗力是目前人们非常感兴趣的一个课题，对生物传感器、植入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，但仍然缺乏纳米和分子水平上对防污机制的理解。在这项工作中结合实验和模拟研究将针对这个重要的problem.Intellectual Merit：从最近的模拟和实验研究完成的PI的组，它似乎是一个相关性之间的无污染性能的寡（乙二醇）（OEG）自组装单分子膜（SAMs）和OEG链的水合/灵活性。此外，PI的研究小组首次证明，以磷酸胆碱（PC）或寡聚（PC）基团封端的SAM强烈抵抗非特异性蛋白质吸附。虽然亲水性和中性OEG基团通过氢键形成水合层，但两性离子基团（例如，PC）通过静电相互作用形成水化层。两性离子能够结合大量的水分子，因此是防污材料的潜在优秀候选者。为了在分子水平上提供对不结垢机制的完整和坚实的理解，OEG和PC SAM是两个优秀的模型系统，因为它们是良好控制的，并且通过不同的机制与水相互作用。因此，本论文的工作主要集中在：（a）利用分子模拟技术研究了蛋白质与OEG（或PC）自组装膜相互作用中结合水分子的结构和动力学行为、力-距离曲线以及自由能的变化;（B）利用红外-可见和频产生（SFG）探测OEG（或PC）链周围结合水分子的结构，并确定了OEG（或PC）链周围结合水分子的焓、自由能、从等温滴定量热法（ITC）和表面等离子体共振（SPR）传感器研究蛋白质吸附的熵变，以及（c）研究智能、无污染和生物相容性两性离子羧基甜菜碱材料的独特性质及其对离子强度、pH和温度变化的响应性。这项纳米相关工作的成功将推进我们在分子水平上对防污机制的基本理解，为评估防污材料提供新的标准，并有助于设计新的智能，防污和生物相容性材料。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。虽然不结垢表面对这些技术至关重要，但对不结垢机制的基本理解是发现新的可再生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的群体。本科研究人员将通过当地研究中心完善的外展计划招募，PI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拟议工作中展示的分子产品设计的新概念将成为该课程的主题。此外，知识将通过其他课程传播，如纳米技术前沿和材料的计算模拟和建模”。

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".