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

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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.