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: 0503942
• 负责人: Igal Szleifer
• 金额: $ 21.57万
• 依托单位: Purdue University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-08-01 至 2008-01-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0503942&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.

这项由威斯康星州、西北大学和普渡大学的研究人员参与的合作资助是为了回应向 NSF-EC 征集提交的提案，该征集由材料研究部与欧盟委员会协调主办。最近的实验表明，液晶材料能够探测具有纳米长度尺度的化学或形貌特征的界面结构。液晶检测表面或界面上蛋白质或病毒吸附的能力已被用于开发高效且廉价的生物传感器。这些传感器的工作原理是液晶材料在表面的锚定转变，这是由生物分子或有机体与基底的结合触发的。这种转变导致缺陷的形成，这些缺陷在宏观长度尺度上传播。这种级联缺陷为显着的放大机制提供了基础，使得通过简单的光学手段检测一些结合事件成为可能。 虽然液晶在传感应用中的使用主要集中在固体表面，但最近的研究表明液-液界面也可用于传感，从而为开发更通用的传感设备以及开发能够实现传感的新技术铺平了道路。以纳米级分辨率探究界面结构。 对于定量的（而不是纯粹定性的）此类设备和技术，有必要开发一种理论形式体系，能够提供宏观实验测量（例如光学显微照片）与锚定转变以及发生在特定位置的特定结合事件之间的直接对应关系。纳米尺度。这种形式本质上是多尺度的，因为它必须能够捕获在几个液晶分子水平上发生的锚定转变，同时能够描述微米长度尺度上缺陷的形成。 提出了一种分层、多尺度建模方法来描述基于液晶的化学和生物传感器。来自美国和欧盟的科学家和工程师组成了一支多元化且独特的团队，他们都具有互补的背景和专业知识。提出了一套精心策划的建模活动，充分利用个人的优势，并利用 M.Olvera、J.de Pablo、I.Szleifer、M.Laso、H.Ottinger 和 D.Theodorou 等团队之间的协同作用。 所提出的分层多尺度方法从水、表面活性剂和肽两亲物负载界面以及液晶的原子模型开始。 残留水平模型用于生物分子。这些模型将是粗粒度的，使用最近提出的非平衡热力学方法。由此产生的粗粒模型将被输入单分子和场论中，以绘制出感兴趣的系统在广泛的参数空间范围内的结构和相行为。这些理论将用于预测界面处纳米结构图案的形成，随后可用于结合特定蛋白质甚至生长因子以捕获细胞。这些理论还将用于提供平均力势和其他相关结构信息，这些信息将被输入到液晶缺陷动力学的场论和晶格玻尔兹曼描述中，在宏观长度尺度上处于平衡状态和超出平衡状态。 这些动态模型的解决方案将在新颖的无网格数值技术的背景下实现。 最终的全球努力将考虑在微观-宏观形式主义中解决整个多尺度系统，这将同时解决有效场中分子的动力学和宏观守恒方程。 智力优点：本提案中设想的传感器系统特别复杂。它们包括多种物质、小分子和大分子、电荷、界面，并且经常在远离平衡的情况下遇到。 它们表现出丰富的结构、相位和动态行为，跨越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仅限于本提案中考虑的系统的选定的、孤立的元素或组件。在分子水平上描述生物分子对肽两亲物和表面活性剂负载界面的吸附，以及描述共存液晶材料对纳米尺度和介观长度尺度上的吸附过程的伴随响应，即使有，也很少有先例，充分考虑水动力效应。 该提案描述了一个多管齐下、协调一致的研究计划，将一些最好的、最先进的理论和模拟引入到此类过程的研究中。更广泛的影响：传感器设计已成为科学技术的核心领域。生物科学将大大受益于能够实时检测蛋白质出现的设备，医学将受益于更快、可靠的微量蛋白质传感器，整个社会将受益于廉价且可靠的化学毒素和病毒制剂传感器。 最近发表的报告表明，该提案中要探索的传感器在所有这些方面都提供了不寻常的前景。 此类报告还强调了这样一个事实：只有通过开发详细的多尺度模型以及对此类系统在不同长度和时间尺度上发生的过程的基本了解，才能充分实现基于液晶的传感设备的有用性和前景。该项目中将开发的多尺度形式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液晶的定量技术来探测界面的结构和特性。