Biomedical subjects

Aleksandr Noy

Publications and source records attributed to Aleksandr Noy.

12 recordsLinked to original sources

PubMed2006

Ultrafast gas chromatography on single-wall carbon nanotube stationary phases in microfabricated channels.

The key to rapid temperature programmed separations with gas chromatography are a fast, low-volume injection and a short microbore separation column with fast resistive heating. One of the major problems with the reduction of column dimensions for micro gas chromatography is the availability of a stationary phase that provides good separation performance. In this report, we present the first integration of single-wall carbon nanotubes (SWNTs) as a stationary phase into 100 mum x 100 mum square and 50-cm-long microfabricated channels. The small size of this column with integrated resistive heater and the robustness of the SWNT phase allow for fast temperature programming of up to 60 degrees C/s. A combination of the fast temperature programming and the narrow peak width of small-volume injections that can be obtained from a high-speed, dual-valve injection system allows for rapid separations of gas mixtures. We demonstrate highly reproducible separations of four-compound test mixtures on these columns in less than 1 s using fast temperature programming.

Journal Article↗

PubMed2006

Fast mass transport through sub-2-nanometer carbon nanotubes.

We report gas and water flow measurements through microfabricated membranes in which aligned carbon nanotubes with diameters of less than 2 nanometers serve as pores. The measured gas flow exceeds predictions of the Knudsen diffusion model by more than an order of magnitude. The measured water flow exceeds values calculated from continuum hydrodynamics models by more than three orders of magnitude and is comparable to flow rates extrapolated from molecular dynamics simulations. The gas and water permeabilities of these nanotube-based membranes are several orders of magnitude higher than those of commercial polycarbonate membranes, despite having pore sizes an order of magnitude smaller. These membranes enable fundamental studies of mass transport in confined environments, as well as more energy-efficient nanoscale filtration.

Journal Article↗

PubMed2006

Strength of multiple parallel biological bonds.

Multivalent interactions play a critical role in a variety of biological processes on both molecular and cellular levels. We have used molecular force spectroscopy to investigate the strength of multiple parallel peptide-antibody bonds using a system that allowed us to determine the rupture forces and the number of ruptured bonds independently. In our experiments the interacting molecules were attached to the surfaces of the probe and sample of the atomic force microscope with flexible polymer tethers, and the unique mechanical signatures of the tethers determined the number of ruptured bonds. We show that the rupture forces increase with the number of interacting molecules and that the measured forces obey the predictions of a Markovian model for the strength of multiple parallel bonds. We also discuss the implications of our results to the interpretation of force spectroscopy measurements in multiple bond systems.

Antibodies↗

PubMed2006

Controlled electrostatic gating of carbon nanotube FET devices.

Carbon nanotube transistors are a promising platform for the next generation of nonoptical biosensors. However, the exact nature of the biomolecule interactions with nanotubes in these devices remains unknown, creating one of the major obstacles to their practical use. We assembled alternating layers of oppositely charged polyelectrolytes on the carbon nanotube transistors to mimic gating of these devices by charged molecules. The devices showed reproducible oscillations of the transistor threshold voltage depending on the polarity of the outer polymer layer in the multilayer film. This behavior shows excellent agreement with the predictions of a simple electrostatic model. Finally, we demonstrate that complex interactions of adsorbed species with the device substrate and the surrounding electrolyte can produce significant and sometimes unexpected effects on the device characteristics.

Biosensing Techniques↗

PubMed2006

High-resolution ab initio three-dimensional x-ray diffraction microscopy.

Coherent x-ray diffraction microscopy is a method of imaging nonperiodic isolated objects at resolutions limited, in principle, by only the wavelength and largest scattering angles recorded. We demonstrate x-ray diffraction imaging with high resolution in all three dimensions, as determined by a quantitative analysis of the reconstructed volume images. These images are retrieved from the three-dimensional diffraction data using no a priori knowledge about the shape or composition of the object, which has never before been demonstrated on a nonperiodic object. We also construct two-dimensional images of thick objects with greatly increased depth of focus (without loss of transverse spatial resolution). These methods can be used to image biological and materials science samples at high resolution with x-ray undulator radiation and establishes the techniques to be used in atomic-resolution ultrafast imaging at x-ray free-electron laser sources.

Algorithms↗

PubMed2005

Dynamic force spectroscopy of parallel individual Mucin1-antibody bonds.

We used atomic force microscopy to measure the binding forces between Mucin1 (MUC1) peptide and a single-chain variable fragment (scFv) antibody selected from a scFv library screened against MUC1. This binding interaction is central to the design of molecules used for targeted delivery of radioimmunotherapeutic agents for prostate and breast cancer treatment. Our experiments separated the specific binding interaction from nonspecific interactions by tethering the antibody and MUC1 molecules to the atomic force microscope tip and sample surface with flexible polymer spacers. Rupture force magnitude and elastic characteristics of the spacers allowed identification of the rupture events corresponding to different numbers of interacting proteins. We used dynamic force spectroscopy to estimate the intermolecular potential widths and equivalent thermodynamic off rates for monovalent, bivalent, and trivalent interactions. Measured interaction potential parameters agree with the results of molecular docking simulation. Our results demonstrate that an increase of the interaction valency leads to a precipitous decline in the dissociation rate. Binding forces measured for monovalent and multivalent interactions match the predictions of a Markovian model for the strength of multiple uncorrelated bonds in a parallel configuration. Our approach is promising for comparison of the specific effects of molecular modifications as well as for determination of the best configuration of antibody-based multivalent targeting agents.

Amino Acid Sequence↗

PubMed2005

Persistence length control of the polyelectrolyte layer-by-layer self-assembly on carbon nanotubes.

We have studied layer-by-layer polyelectrolyte self-assembly on pristine individual single-wall carbon nanotubes as a function of solution ionic strength. We report the existence of an ionic strength threshold for the deposition, below which the majority of nanotubes remain uncoated. Once the ionic strength reaches the threshold value, the majority of the individual nanotubes become coated with polyelectrolytes. Our results indicate that the self-assembly process likely involves wrapping of polymer chains around nanotubes and that the polymer chain's ability to bend in order to accommodate the nanotube curvature is one of the critical parameters controlling layer-by-layer electrostatic self-assembly on these one-dimensional templates.

Electrochemistry↗

PubMed2005

Functional one-dimensional lipid bilayers on carbon nanotube templates.

Use of biological machines and environments in novel bioinorganic nanostructures is critical for development of new types of biosensors, bio-NEMS devices, and functional materials. Lipid bilayers that mimic a cell membrane have already played an important role in such applications. We present supported lipid bilayers that spontaneously assemble in a continuous nanoshell around a template of a carbon nanotube wrapped with hydrophilic polymer cushion layers. We demonstrate that such 1-D lipid membranes are fluid and can heal defects, even over repeated damage-recovery cycles. A simple diffusion model can describe mobility of lipid molecules in these 1-D nanoshells. These structures could lead to the development of new classes of biosensors and bioelectronic devices.

Biomimetic Materials↗

PubMed2004

Layer-by-Layer electrostatic self-assembly of polyelectrolyte nanoshells on individual carbon nanotube templates.

Carbon nanotubes have been featured prominently in the nanotechnology research for some time, yet robust strategies for noncovalent chemical modification of the nanotube surface are still missing. Such strategies are essential for the creation of functional device architectures. Here, we present a new general procedure for carbon nanotube modification based on polyelectrolyte layer-by-layer assembly. We have built multilayer structures around individual carbon nanotube bridges by first modifying the nanotube surface with a pyrene derivative followed by layer-by-layer deposition of polyelectrolyte macroions on the nanotube. Transmission electron microscopy and scanning confocal fluorescence microscopy images confirm the formation of nanometer-thick amorphous polymer nanoshells around the nanotubes. These multilayer polyelectrolyte shells on individual carbon nanotubes introduce nearly unlimited opportunities for the incorporation of various functionalities into nanotube devices, which, in turn, opens up the possibility of building more complex multicomponent structures.

Journal Article↗

PubMed2004

Mechanism of DNA compaction by yeast mitochondrial protein Abf2p.

We used high-resolution atomic force microscopy to image the compaction of linear and circular DNA by the yeast mitochondrial protein Abf2p, which plays a major role in packaging mitochondrial DNA. Atomic force microscopy images show that protein binding induces drastic bends in the DNA backbone for both linear and circular DNA. At a high concentration of Abf2p DNA collapses into a tight nucleoprotein complex. We quantified the compaction of linear DNA by measuring the end-to-end distance of the DNA molecule at increasing concentrations of Abf2p. We also derived a polymer statistical mechanics model that provides a quantitative description of compaction observed in our experiments. This model shows that sharp bends in the DNA backbone are often sufficient to cause DNA compaction. Comparison of our model with the experimental data showed excellent quantitative correlation and allowed us to determine binding characteristics for Abf2p. These studies indicate that Abf2p compacts DNA through a simple mechanism that involves bending of the DNA backbone. We discuss the implications of such a mechanism for mitochondrial DNA maintenance and organization.

Binding Sites↗

PubMed2003

Entropic barriers in nanoscale adhesion studied by variable temperature chemical force microscopy.

Intermolecular interactions drive the vast majority of condensed phase phenomena from molecular recognition to protein folding to particle adhesion. Complex energy barriers encountered in these interactions include contributions from van der Waals forces, hydrogen bonding, and solvent medium. With the spectacular exception of hydrophobic interactions, contributions from the medium are usually considered secondary. We report a variable temperature force microscopy study of the interactions between several hydrogen bonds in different solvents that challenges this point of view. Surprisingly, we observed an increase in the strength of the interaction between carboxylic acid groups in ethanol as the temperature increased. Moreover, when we switched to a nonpolar solvent we observed the opposite behavior: The binding force decreased as the temperature increased. Kinetic model of bond dissociation provided quantitative interpretation of our measurements. We attributed the observed phenomena to a large entropic contribution from the ordered solvent layers that are forming on the probe and sample surfaces upon detachment. The observed reversal in the force vs temperature trend is a manifestation of a transition between thermodynamic and kinetic regimes of unbinding predicted by the model. Our results indicate that entropic barriers dominated by the interactions of solvent molecules with the surface exist in a much wider variety of systems than previously thought.

Carboxylic Acids↗

PubMed2003

Packaging of single DNA molecules by the yeast mitochondrial protein Abf2p.

Mitochondrial and nuclear DNA are packaged by proteins in a very different manner. Although protein-DNA complexes called "nucleoids" have been identified as the genetic units of mitochondrial inheritance in yeast and man, little is known about their physical structure. The yeast mitochondrial protein Abf2p was shown to be sufficient to compact linear dsDNA, without the benefit of supercoiling, using optical and atomic force microscopy single molecule techniques. The packaging of DNA by Abf2p was observed to be very weak as evidenced by a fast Abf2p off-rate (k(off) = 0.014 +/- 0.001 s(-1)) and the extremely small forces (<0.6 pN) stabilizing the condensed protein-DNA complex. Atomic force microscopy images of individual complexes showed the 190-nm structures are loosely packaged relative to nuclear chromatin. This organization may leave mtDNA accessible for transcription and replication, while making it more vulnerable to damage.

Binding Sites↗