Responsive Tethered Polymer Layers: Protein Adsorption, Phase Transition and Interactions

Igal G. SzleiferPurdue大学“响应系绳聚合物层：蛋白质吸附，相变和相互作用”这项研究的目的是对系绳聚合物层的行为进行理论研究，这些聚合物层可以在实验控制变量（如温度，pH值或盐浓度）的变化下可逆或不可逆地改变其性质。了解这些层的行为是迈向无污垢表面、生物相容性材料、药物输送系统和传感器等分子设计的基本步骤。这项工作将集中在聚合物层的结构和热力学变化以及这些变化如何影响：(i)层吸附或拒绝蛋白质（或纳米颗粒）吸附的能力以及（ii）聚合物层与其他表面的相互作用。理论研究将以PI开发的分子理论为基础，该理论已成功应用于研究蛋白质吸附的热力学和动力学，以及栓系聚合物层的结构和热力学性质。此外，原子分子动力学模拟将用于研究pH敏感肽。这项研究将与两个实验组密切合作进行。要研究的特定聚合物体系包括：1)热响应聚合物层；2)带电荷基团和生物活性配体功能化的聚环氧乙烷（PEO）； 3) PEO与pH敏感肽的嵌段共聚物。前两个系统旨在控制蛋白质吸附和从吸附表面可逆切换到非吸附表面的能力。pH敏感肽旨在控制聚合物修饰层与脂质双分子层或其他疏水表面/界面的粘附。这项研究活动是工程学、物理学、化学和生物学的交叉领域。它结合了：1)对复杂系统的基本理解，其中相关长度尺度为纳米，时间尺度从毫秒到小时不等；2)在生物材料、药物载体和纳米传感器等设计中的实际应用。因此，这项研究将结合原子计算机模拟来了解详细的相互作用和溶剂化与分子理论，使用比模拟更粗粒度的模型。此外，分子方法能够系统地研究大系统的动力学、结构和热力学性质。正在进行的与教授的实验小组的合作。Thompson（普渡大学）和Genzer (NCSA)，凭借其已经证明的记录，为在所有阶段的实际和应用环境中保持理论工作提供了必要的框架。拟议活动的更广泛影响该研究计划将涉及研究生和本科生的参与。特别值得一提的是，PI计划通过参加成功的MARC/AIM计划和将研究项目与普渡大学研究生院少数民族计划管理的“生物医学科学多样性暑期研究所”联系起来，吸引来自代表性不足的少数民族的本科研究学生。通过与Weaver教授（普渡大学化学教育）的合作，研究工作将进一步融入本科教育，并在后期甚至融入高中教育。这种整合将导致多媒体和交互式DVD的发展，其中包含研究数据，以应用在课堂上学到的概念。研究结果将在PI的网页上以流行版本发布。课程将为非专家提供分子理论应用和计算机模拟的教程，以及对研究成果及其与工程和科学许多领域的相关性的简单描述。

Igal G. SzleiferPurdue University "Responsive Tethered Polymer Layers: Protein Adsorption, Phase Transition and Interactions"The aim of this research is the theoretical study of the behavior of tethered polymer layers that can reversibly or irreversibly switch their properties upon change in an experimentally controlled variable, such as temperature, pH or salt concentration. The understanding of the behavior of these layers is a fundamental step towards the molecular design of non-fouling surfaces, biocompatible materials, drug delivery systems and sensors among many others. The work will concentrate on the structural and thermodynamic changes in the polymer layers and how these changes affect: (i) The ability of the layer to adsorb or reject protein (or nanoparticle) adsorption and (ii) The interactions of the polymer layer with other surfaces. The theoretical studies will be based on a molecular theory, developed by the PI, that has been successfully applied to study the thermodynamics and kinetic of protein adsorption, as well as the structural and thermodynamic properties of tethered polymer layers. Further, atomistic molecular dynamics simulations will be used to study pH sensitive peptides. The research will be carried out in close collaboration with two experimental groups. The specific polymeric systems to be studied include: 1) thermo-responsive polymer layers, 2) poly-ethylene oxide (PEO) functionalized with charged moieties and with bioactive ligands and 3) block copolymers of PEO with pH sensitive peptides. The first two systems are aimed at controlling protein adsorption and the ability to reversibly switch from adsorbing to non-adsorbing surfaces. The pH sensitive peptides are aimed at controlling the adhesion of the polymer modified layers with lipid bilayers or other hydrophobic surfaces/interfaces.Intellectual merit of the proposed activityThis research activity is at the intersection of engineering, physics, chemistry and biology. It combines: 1) The fundamental understanding of complex systems where the relevant length scale is nanometers with time scales that range from milliseconds to hours, with 2) The practical application in the design of biomaterials, drug carriers and nanosensors among others. Thus, this research would combine atomistic computer simulations to understand detailed interactions and solvation with molecular theory that uses more coarse-grained models than the simulations. Furthermore, the molecular approach enables the systematic study of the kinetics, structural and thermodynamic properties of large systems. The ongoing collaborations with the experimental groups of Profs. Thompson (Purdue) and Genzer (NCSA), with its already proven track record, provides the necessary framework to maintain the theoretical work in a practical and applied environment at all stages.Broader impact from the proposed activityThe research program will involve the participation of graduate and undergraduate students. In particular, the PI plans to attract undergraduate research students from underrepresented minorities by participating in the successful MARC/AIM program and by linking the research projects with the "Summer Institute for Diversity in Biomedical Science", both administered by the Minority Program of the Graduate School at Purdue University. The research work will be further integrated into undergraduate education, and at a later stage even high school education, by collaboration with Prof. Weaver (Chemical Education, Purdue). This integration will result in the development of multimedia and interactive DVD's that incorporate research data to apply the concepts learned in the classroom.The research findings will be available in a popular version in the web page of the PI. There will be tutorials for the application of the molecular theory and computer simulations for the non-experts, as well as a simple description of the research outcomes and their relevance to many fields in engineering and science.