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

响应性束缚聚合物层：蛋白质吸附、相变和相互作用

• 批准号: 0338377
• 负责人: Igal Szleifer
• 金额: $ 30万
• 依托单位: Purdue University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-12-15 至 2007-11-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0338377&HistoricalAwards=false
• 关键词: Responsive; Tethered; Polymer; Layers; Protein

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.

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.对这些层的行为的理解是迈向非污染表面，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。这项工作将集中于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（或纳米粒子）吸附的能力以及（ii）聚合物层与其他表面的相互作用。理论研究将基于由PI开发的分子理论，该理论已成功地用于研究蛋白质吸附的热力学和动力学，以及链球菌聚合物层的结构和热力学特性。此外，原子分子动力学模拟将用于研究pH敏感肽。该研究将与两个实验组密切合作进行。要研究的特定聚合系统包括：1）热响应性聚合物层，2）用带电的部分和生物活性配体和3）PEO的PEO共聚物与pH敏感肽的PEO共聚物。前两个系统旨在控制蛋白质的吸附以及可逆切换到非吸附表面的能力。 pH敏感肽旨在控制聚合物改性层与脂质双层或其他疏水表面/接口的粘附。拟议的活动活动的智能优点在工程，物理，化学，化学和生物学的交集上。它结合在一起：1）对复杂系统的基本理解，其中相关长度尺度是纳米，其时间尺度的范围从毫秒到小时，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，以了解详细的相互作用和溶剂化与分子理论，该分子理论使用比模拟更粗糙的模型。此外，分子方法可以系统地研究大系统的动力学，结构和热力学特性。与教授实验组的持续合作。汤普森（Purdue）和Genzer（NCSA）凭借其已证实的记录，为在各个阶段的实用和应用环境中维持理论工作提供了必要的框架。提议的活动对研究计划的影响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计划，并通过将研究项目与“生物医学科学多样性研究所”联系起来，从而吸引来自代表性不足的少数民族的本科生研究学生，均由普渡大学研究生院的少数民族计划管理。研究工作将通过与Weaver教授（化学教育，普渡大学）合作，将进一步纳入本科教育，甚至在稍后的高中教育中。这种整合将导致多媒体和交互式DVD的开发，并结合了研究数据以应用课堂上学到的概念。研究结果将在PI网页中的流行版本中获得。将有一些教程，用于将分子理论和计算机模拟应用于非专家，以及对研究结果的简单描述及其与工程和科学领域的许多领域的相关性。