Collaborative Research: NSF-EC Cooperative Activity in Computational Materials Research: Multiscale Modeling of Nanostructured Interfaces for Biological Sensors

合作研究： NSF-EC 计算材料研究中的合作活动：生物传感器纳米结构界面的多尺度建模

• 批准号: 0757137
• 负责人: Igal Szleifer
• 金额: $ 8.29万
• 依托单位: Northwestern University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-07-31 至 2009-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0757137&HistoricalAwards=false
• 关键词: Collaborative; Research; NSF; EC; Cooperative

This collaborative grant involving researchers at Wisconsin, Northwestern and Purdue has been made in response to a proposal submitted to the NSF-EC solicitation sponsored by the Division of Materials Research in coordination with the European Commission.Recent experiments have shown that liquid crystalline materials are capable of probing the structure of interfaces having chemical or topographical features of nanometer length-scales. The ability of liquid crystals to detect the adsorption of proteins or viruses at surfaces or interfaces has been exploited for development of highly effective and inexpensive biological sensors. The principle of operation for these sensors is an anchoring transition of the liquid crystal material at a surface, triggered by the binding of a biological molecule or organism to a substrate. This transition leads to formation of defects, which propagate over macroscopic length scales. This cascade of defects provides the basis for a remarkable amplification mechanism, making possible the detection of a few binding events by simple optical means. While the use of liquid crystals for sensing applications has been focused on solid surfaces, recent studies suggest that liquid-liquid interfaces could also be used for sensing, thereby paving the way for development of more versatile sensing devices, and development of novel technologies capable of interrogating the structure of interfaces with nanometer level resolution. For such devices and technologies to be quantitative (as opposed to purely qualitative), it will be necessary to develop a theoretical formalism capable of providing a direct correspondence between macroscopic experimental measurements (e.g. optical micrographs) and anchoring transitions and specific binding events occurring at the scale of nanometers. That formalism is inherently multi-scale, in that it must be capable of capturing anchoring transitions occurring at the level of a few liquid crystal molecules while being able to describe the formation of defects over micrometer length scales. A hierarchical, multi-scale modeling approach is proposed for description of liquid-crystal based chemical and biological sensors. A diverse and unique team of scientists and engineers from the US and the EC has been assembled, all of them with complementary backgrounds and expertise. A carefully orchestrated set of modeling activities is proposed which capitalizes on the strengths of individuals and exploits synergisms between the groups of M.Olvera, J.de Pablo, I.Szleifer, M.Laso, H.Ottinger, and D.Theodorou. The proposed hierarchical multi-scale approach starts from atomistic models of water, surfactant and peptide amphiphile laden interfaces, and liquid crystals. Residue-level models are used for biological molecules. These models will be coarse grained, using recently proposed methods from non-equilibrium thermodynamics. The resulting coarse grain models will be fed into single-molecule and field theories to map out the structure and phase behavior of the systems of interest over wide ranges of parameter space. The theories will be used to predict the formation of nanostructured patterns at interfaces, which can subsequently be exploited to bind specific proteins and even growth factors for cell capture. The theories will also be used to provide potentials of mean force and other relevant structural information, which will be fed into field-theoretic and lattice Boltzmann descriptions of defect dynamics in liquid crystals, over macroscopic length scales both at and beyond equilibrium. Solution of these dynamic models will be implemented within the context of novel, grid-less numerical techniques. A final, global effort will consider solution of the entire multi-scale system within a micro-macro formalism that will simultaneously resolve the dynamics of molecules in effective fields and the macroscopic conservation equations. Intellectual Merit: The sensor systems envisaged in this proposal are particularly complex. They include multiple species, small and large molecules, charges, interfaces, and are often encountered in far from equilibrium situations. They exhibit a rich structural, phase and dynamical behavior that spans many length and time scales. Given this complexity, past theoretical and numerical studies have been largely limited to select, isolated elements or components of the systems considered in this proposal. There are few, if any precedents for describing the adsorption of biological molecules to peptide amphiphile and surfactant laden interfaces at a molecular level, and for describing the concomitant response of a coexisting liquid crystalline material to that adsorption process over nanoscopic and mesoscopic length scales, with full consideration of hydrodynamic effects. This proposal describes a multi-pronged, concerted plan of research that brings some of the best, state-of-the-art theory and simulation to the study of such processes. Broader Impacts: Sensor design has become an area of central importance to science and technology. The biological sciences will benefit considerably from devices capable of detecting the occurrence of proteins in real time, medicine will benefit from faster, reliable sensors for minute amounts of proteins, and society in general will benefit from inexpensive and reliable sensors for chemical toxins and viral agents. Recent published reports indicate that the sensors to be explored in this proposal offer unusual promise on all of those fronts. Such reports also underline the fact that the usefulness and promise of liquid-crystal based sensing devices can only be fully realized by developing detailed multi-scale models and a fundamental understanding of the processes that occur in such systems over various length and time scales. The multi-scale formalism to be developed in this project will not only facilitate considerably the design and development of sensors, but will also permit development of quantitative, liquid-crystal based techniques to probe the structure and properties of interfaces.

这项合作赠款涉及威斯康星州，西北和普渡大学的研究人员，是为了回应由材料研究部与欧洲委员会协调的NSF-EC招标提出的提案。探测具有纳米长度尺度化学或地形特征的界面结构。已经利用了液晶检测蛋白质或病毒在表面或界面上的吸附的能力，以开发高效和廉价的生物传感器。这些传感器的操作原理是液晶材料在表面的锚定过渡，这是由生物分子或生物与底物的结合触发的。这种转变导致缺陷的形成，在宏观长度尺度上传播。这种级联缺陷为一种显着的放大机制提供了基础，从而使通过简单的光学手段来检测一些几个结合事件。 虽然将液晶用于传感应用集中在固体表面上，但最近的研究表明，液体液体界面也可以用于感测，从而为开发更通用的传感设备的开发铺平了道路，并开发了能够开发能够开发的新技术通过纳米水平分辨率询问接口的结构。 对于这样的设备和技术的定量（与纯粹的定性相反），有必要开发一种理论形式主义，能够在宏观实验测量（例如光学显微照片）之间提供直接对应关系（例如，光学显微照片）和锚定过渡和在发生的特定结合事件纳米尺度。这种形式主义本质上是多尺度的，因为它必须能够捕获在几个液晶分子水平上发生的锚定过渡，同时能够描述在微米长度尺度上形成缺陷的形成。 提出了一种分层的多尺度建模方法，用于描述基于液晶的化学和生物传感器。一支来自美国和EC的科学家和工程师的多元化和独特的团队都已组装，所有这些团队都具有互补的背景和专业知识。提出了一组精心策划的建模活动，该活动利用了个人的优势，并利用了M.olvera，J.De Pablo，I.Szleifer，M.Laso，M.Laso，H.Ottinger和D.Theodorou之间的协同作用。 所提出的分层多尺度方法始于水，表面活性剂和肽两亲物质界面以及液晶的原子模型。 残基级模型用于生物分子。这些模型将使用最近提出的非平衡热力学方法进行粗粒。所得的粗粒模型将被馈入单分子和场理论，以绘制出广泛的参数空间范围内感兴趣系统的结构和相位行为。这些理论将用于预测界面处的纳米结构模式的形成，随后可以利用该图案以结合特定的蛋白质甚至生长因子以绑定细胞捕获。这些理论还将用于提供平均力和其他相关结构信息的潜力，这些信息将被赋予液晶缺陷动力学的现场理论和晶格玻尔兹曼，在宏观长度上均超过平衡的宏观长度。 这些动态模型的解决方案将在新颖无网格的数值技术的背景下实现。 最终的全球努力将考虑在微观形式主义中的整个多尺度系统的解决方案，该系统将同时解决有效领域和宏观保护方程中分子的动力学。 智力优点：该提案中设想的传感器系统特别复杂。它们包括多种物种，小分子和大分子，电荷，界面，通常在远离平衡情况下遇到。 它们表现出丰富的结构，相和动力学行为，跨越了许多长度和时间尺度。鉴于这种复杂性，过去的理论和数值研究在很大程度上被限制为选择该提案中考虑的系统的孤立元素或组成部分。如果有任何先例描述生物分子在分子水平上吸附到肽两亲物和表面活性剂载体界面的吸附，以及描述共存液晶材料对与纳米和介导长度尺度相关的液晶材料的同时响应完全考虑流体动力效应。 该提案描述了一项多管齐的一致研究计划，该计划将一些最好的，最先进的理论和模拟带入了此类过程的研究。更广泛的影响：传感器设计已成为对科学技术的重要性领域。生物科学将从能够实时检测蛋白质发生的设备中受益匪浅，医学将从更快，可靠的传感器中受益于微量蛋白质，而社会通常将从化学毒素和病毒剂的廉价和可靠的传感器中受益。 最近发表的报告表明，该提案中要探索的传感器对所有这些方面都提供了异常的希望。 此类报告还强调了这样一个事实，即只有通过开发详细的多尺度模型以及对在各种长度和时间尺度上发生此类系统中发生的过程的基本了解，才能完全实现基于液体结晶的传感设备的有用性和希望。该项目中要开发的多尺度形式主义不仅将大大促进传感器的设计和开发，而且还将允许开发基于定量的，基于液晶的技术来探测接口的结构和特性。