Joel M. Schnur

Lipid Tubules: A Paradigm for Molecularly Engineered Structures

The use of molecular self-assembly to fabricate microstructures suitable for advanced material development is described. Templating techniques that transform biomolecular self-assemblies into rugged and stable nano- and microstructures are described. By using a lipid-based microcylinder (tubule) as a paradigm, the path followed from research and development to emerging technological applications is detailed. This process includes modification of the lipid molecular structure, the formation and subsequent characterization of cylindrical microstructures, the use of these structures as templates for metallization, and the characterization and assessment of these hollow metal microcylinders for several potential applications.

Diacetylenic lipid tubules: experimental evidence for a chiral molecular architecture.

Molecular self-assembly is of key importance for the rational design of advanced materials. To investigate the causal relation between molecular structure and the consequent self-assembled microstructure, self-assembled tubules of diacetylenic lipids were studied. Circular-dichroism studies give experimental evidence that the formation of tubules is driven by chiral molecular packing, in agreement with recent theories of tubules. On the basis of these results, a molecular mechanism for the formation of tubules is proposed.

Lipid-based tubule microstructures☆

Abstract Hollow tubule-shaped microstructures have been fabricated by self-organization of polymerizable diacetylenic phospholipid molecules. These microstructures have potential applications in a number of areas in materials science. A wide range of positional isomers of the diacetylenic lipids have been synthesized and all form tubules. A process for the deposition of thin metal coatings onto the exterior surfaces of the tubules has been developed. Results of spectroscopic and microscopic investigations of the lipids and microstructures are presented. Future issues important to the assessment of the ultimate utility of these materials are also presented.

Theory of cylindrical tubules and helical ribbons of chiral lipid membranes

We present a general theory for the equilibrium structure of cylindrical tubules and helical ribbons of chiral lipid membranes. This theory is based on a continuum elastic free energy that permits variations in the direction of molecular tilt and in the curvature of the membrane. The theory shows that the formation of tubules and helical ribbons is driven by the chirality of the membrane. Tubules have a first-order transition from a uniform state to a helically modulated state, with periodic stripes in the tilt direction and ripples in the curvature. Helical ribbons can be stable structures, or they can be unstable intermediate states in the formation of tubules.

Using a Resequencing Microarray as a Multiple Respiratory Pathogen Detection Assay

ABSTRACT Simultaneous testing for detection of infectious pathogens that cause similar symptoms (e.g., acute respiratory infections) is invaluable for patient treatment, outbreak prevention, and efficient use of antibiotic and antiviral agents. In addition, such testing may provide information regarding possible coinfections or induced secondary infections, such as virally induced bacterial infections. Furthermore, in many cases, detection of a pathogen requires more than genus/species-level resolution, since harmful agents (e.g., avian influenza virus) are grouped with other, relatively benign common agents, and for every pathogen, finer resolution is useful to allow tracking of the location and nature of mutations leading to strain variations. In this study, a previously developed resequencing microarray that has been demonstrated to have these capabilities was further developed to provide individual detection sensitivity ranging from 101 to 103 genomic copies for more than 26 respiratory pathogens while still retaining the ability to detect and differentiate between close genetic neighbors. In addition, the study demonstrated that this system allows unambiguous and reproducible sequence-based strain identification of the mixed pathogens. Successful proof-of-concept experiments using clinical specimens show that this approach is potentially very useful for both diagnostics and epidemic surveillance.

Pressure induced changes in liquid alkane chain conformation

Conformations of n‐alkane molecules in the liquid state have been studied as a function of temperature and pressure using Raman scattering. Observations of conformationally sensitive Raman bands in hexane, heptane, octane, and hexadecane reveal no sign of the pressure‐induced effects in polyethylene. Instead the Raman intensities indicate chain kinking as a function of pressure—a dramatic effect in the shorter chains, a slight effect for hexadecane. A theory based on considerations of conformational energy and translational entropy is presented which explains these effects qualitatively.

Shape selection in chiral self-assembly

Many biological and synthetic materials self-assemble into helical or twisted aggregates. The shape is determined by a complex interplay between elastic forces and the orientation and chirality of the constituent molecules. We study this interplay through Monte Carlo simulations, with an accelerated algorithm motivated by the growth of an aggregate out of solution. The simulations show that the curvature changes smoothly from cylindrical to saddlelike as the elastic moduli are varied. Remarkably, aggregates of either handedness form from molecules of a single handedness, depending on the molecular orientation.

Automated identification of multiple micro-organisms from resequencing DNA microarrays

There is an increasing recognition that detailed nucleic acid sequence information will be useful and even required in the diagnosis, treatment and surveillance of many significant pathogens. Because generating detailed information about pathogens leads to significantly larger amounts of data, it is necessary to develop automated analysis methods to reduce analysis time and to standardize identification criteria. This is especially important for multiple pathogen assays designed to reduce assay time and costs. In this paper, we present a successful algorithm for detecting pathogens and reporting the maximum level of detail possible using multi-pathogen resequencing microarrays. The algorithm filters the sequence of base calls from the microarray and finds entries in genetic databases that most closely match. Taxonomic databases are then used to relate these entries to each other so that the microorganism can be identified. Although developed using a resequencing microarray, the approach is applicable to any assay method that produces base call sequence information. The success and continued development of this approach means that a non-expert can now perform unassisted analysis of the results obtained from partial sequence data.

Testing and Validation of High Density Resequencing Microarray for Broad Range Biothreat Agents Detection

Rapid and effective detection and identification of emerging microbiological threats and potential biowarfare agents is very challenging when using traditional culture-based methods. Contemporary molecular techniques, relying upon reverse transcription and/or polymerase chain reaction (RT-PCR/PCR) provide a rapid and effective alternative, however, such assays are generally designed and optimized to detect only a limited number of targets, and seldom are capable of differentiation among variants of detected targets. To meet these challenges, we have designed a broad-range resequencing pathogen microarray (RPM) for detection of tropical and emerging infectious agents (TEI) including biothreat agents: RPM-TEI v 1.0 (RPM-TEI). The scope of the RPM-TEI assay enables detection and differential identification of 84 types of pathogens and 13 toxin genes, including most of the class A, B and C select agents as defined by the Centers for Disease Control and Prevention (CDC, Atlanta, GA). Due to the high risks associated with handling these particular target pathogens, the sensitivity validation of the RPM-TEI has been performed using an innovative approach, in which synthetic DNA fragments are used as templates for testing the assays limit of detection (LOD). Assay specificity and sensitivity was subsequently confirmed by testing with full-length genomic nucleic acids of selected agents. The LOD for a majority of the agents detected by RPM-TEI was determined to be at least 104 copies per test. Our results also show that the RPM-TEI assay not only detects and identifies agents, but is also able to differentiate near neighbors of the same agent types, such as closely related strains of filoviruses of the Ebola Zaire group, or the Machupo and Lassa arenaviruses. Furthermore, each RPM-TEI assay results in specimen-specific agent gene sequence information that can be used to assess pathogenicity, mutations, and virulence markers, results that are not generally available from multiplexed RT-PCR/PCR-based detection assays.

Biologically engineered microstructures : controlled release applications

The area of self-assembled ultrafine particulate-based composites (nano composites) has been a major thrust in advanced material development. In this paper we report on the application of biologically derived, self-assembled cylindrical microstructures to form advanced composite materials for controlled release applications. These microstructures (we call them tubules) have many applications in the material sciences. This paper will focus on the potential for rationally controlling the fabrication of submicron microstructures for controlled release applications.