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May 17, 2006 2006 NSLS-CFN Joint Users' Meeting WorkshopPlatforms for the Integration of Biological Systems into Nanomaterials and InterfacesHybrid systems, built from inorganic and biological/organic nano- and micro-elements, offer unique properties and can lead to creation of novel materials and devices with tailored functions. Although there is much promise for a variety of applications, ranging from nano-architectured devices to biosensing and to tissue engineering, recent research developments demonstrate that integration of elements of different natures in one system is a challenging and complex problem requiring multidisciplinary efforts. Indeed, the interactions of elements of various types, cross-compatibility and the response towards environmental conditions might be substantially different. The workshop, held on May 17, 2006 at Brookhaven National Laboratory, as part of the Joint User's Meeting of the National Synchrotron Light Source (NSLS) and Center for Functional Nanomaterials (CFN), brought together interdisciplinary researchers working on synthesis/assembling hybrid systems and the state-of-the-art characterization techniques, including atomic force microscopy, X-ray methods, and single particle/molecular imaging methods. The morning session was opened by Hiroshi Matsui of City University of New York with a presentation on the use of peptide/protein assemblies in material synthesis and device fabrication. Matsui's group has been developing an assembling strategy that utilizes synthetic peptide-based nanotubes (antibody) and their functionalization with various recognition components (antigen). These building blocks assemble three-dimensional nanoscale architectures from metal and semiconductor nanocrystals. Recently, Matsui's group synthesized nanotubes with certain peptide sequences for selective growth of specific nanocrystals via biomineralization. By controlling the peptide conformation or peptide geometry, nanocrystals of different sizes and shapes can be obtained. For example, the nano-rings mimic Nature and grow crystals at room temperature, which typically requires high temperature to grow by other synthetic methods. Inspired by the interesting questions posed by biomineralization, Elaine Dimasi (BNL) reported the study on the mineralization of self-assembled networks of extracellular matrix proteins. The protein networks are an especially instructive platform for biomineralization, because they incorporate both structured and unstructured proteins; this allows testing the presumed importance of tertiary structure. By measuring biomineral thickness and the elastic modulus using Atomic Force Microscopy (AFM), the group found that thickening and stiffening occurs only on the structured portions of the proteins. Lessons learned from the structure and function of biominerals can be applied to the design and characterization of synthetic functional nanomaterials. Recently, nanoscale materials, including fluorescent nanocrystals, nanoshells, and nanotubes, have been applied for bioimaging applications and the analysis of local nanoenvironment. The current challenges, however, are in the quantitative understating of the relationship between the biochemical environments and the optical properties, and designing optically efficient nano-clusters. Jeeseong Hwang of NIST discussed recent efforts on the optical metrology of single bio-conjugated nanocrystals, bioengineering of bacteriophage-nanocrystal complexes, and assessing of nanoscale molecular delivery systems employing fluorescent nanocrystals encapsulated by lipid molecules. An exciting method for synthesizing a versatile new class of nearly spherical colloidal particles that interact with well-defined non-spherical symmetries was described by David Pine of New York University. These particles are typically several hundreds of nanometers in diameter and have attractive interaction potentials with twofold, threefold, or higher symmetries. Thus, a well-defined "valence" is analogous to atoms: the particles with twofold and fourfold attractive interactive potentials are analogous to sulfur and carbon, respectively, for example. The afternoon session started with a presentation by Erin Lavik from Yale University on applications of nanotechnology to tissue engineering. It was observed that while cells alone often could not recapitulate a tissue, cells seeded on a biodegradable polymer scaffold under the right conditions could. One of the key features in directing cells is to present them with the appropriate microenvironment that includes growth factors, surface molecules, and mechanical forces. The polymer systems might allow for control over a range of length scales from the nanoscale to the macroscale. The research might lead, for example, to direct neural progenitors for repair in the central nervous system. The direct measure of forces between molecules and nano-objects using AFM provides valuable insight on molecular-scale interactions under controllable in-situ conditions. Aleksandr Noy of the Lawrence Livermore National Laboratory discussed the basic physics of the force measurements in molecular systems, focusing on the behavior of a non-covalent bond under external force stress. The presented measurements of the strength of multiple individual Mucin1-antibody bonds demonstrated that force spectroscopy can efficiently probe the thermodynamics and kinetics of intermolecular interactions. The results provided a basis for estimating the strength of multiple uncorrelated biological bonds; this has an implication to the multivalent drug design efforts. Theoretical work on understanding complex systems built from colloidal particles and DNA was presented by Alexei Tkachenko of University of Michigan. In this class of systems, the sequence of single stranded DNA attached to a particle determines its type, and DNA "linkers" induce type-dependent interactions. Even in the simplest case of a binary mixture, the system exhibits surprisingly diverse and unusual phase morphologies, ranging from the diamond lattice to the membrane phase with in-plane square order, and to spontaneous compactification. The "programmable" self-assembly of mesoscopic clusters of such particles with type-dependent interactions is predicted, which is reminiscent of heteropolymer folding problem. The study on the formation of hybrid liquid crystals of DNA and elastin-like peptides by electrostatically driven self-assembly was reported by Helmut Strey of SUNY at Stony Brook. The resulting material exhibits the liquid crystallinity stemming from the DNA while showing thermal sensitivity originating from the peptides. These liquid crystals are a compelling example of a multi-level self-assembly, which is an important process in biology, and show promise as bioinspired materials. In summary, this workshop drew together exciting new results and challenges across the diverse range of systems, from molecular to cellular levels. Various interdisciplinary approaches and techniques that will allow developing a long term platform for integration bio-elements into nanomaterials has been demonstrated and discussed. 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