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

伊加尔湾SzleiferPurdue大学“响应性拴系聚合物层：蛋白质吸附，相变和相互作用“本研究的目的是理论研究拴系聚合物层的行为，该行为可以在实验控制变量（如温度，pH值或盐浓度）变化时可逆或不可逆地切换其属性。对这些层的行为的理解是朝着无污染表面、生物相容性材料、药物递送系统和传感器等的分子设计迈出的基本一步。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）吸附的能力和（ii）聚合物层与其他表面的相互作用。理论研究将基于PI开发的分子理论，该理论已成功应用于研究蛋白质吸附的热力学和动力学，以及拴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小组密切合作进行。待研究的具体聚合物系统包括：1）热响应聚合物层，2）用带电部分和生物活性配体官能化的聚环氧乙烷（PEO）和3）PEO与pH敏感肽的嵌段共聚物。前两个系统的目的是控制蛋白质吸附和可逆地从吸附表面切换到非吸附表面的能力。pH敏感肽的目的是控制聚合物改性层与脂质双层或其他疏水表面/界面的粘附。拟议活动的智力价值这项研究活动是在工程，物理，化学和生物学的交叉点。它结合了：1）对复杂系统的基本理解，其中相关的长度尺度是纳米，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，这项研究将结合联合收割机原子计算机模拟，以了解详细的相互作用和溶剂化与分子理论，使用更粗粒度的模型比模拟。此外，分子方法使系统的动力学，结构和热力学性质的大系统的研究。与教授实验组的持续合作。汤普森（普渡大学）和根策（NCSA），其已经证明的跟踪记录，提供了必要的框架，以保持理论工作在实践和应用环境中的所有阶段。更广泛的影响，从拟议的activityThe研究计划将涉及研究生和本科生的参与。特别是，PI计划通过参加成功的MARC/AIM方案并将研究项目与“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生，这两个项目都由普渡大学研究生院少数民族方案管理。研究工作将进一步融入本科教育，并在稍后阶段，甚至高中教育，通过与教授合作韦弗（化学教育，普渡）。这一整合将导致开发多媒体和交互式DVD，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的网页上以流行的版本提供。将为非专家提供分子理论和计算机模拟应用的教程，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.