Biomedical subjects

Wolfgang Losert

Publications and source records attributed to Wolfgang Losert.

9 recordsLinked to original sources

PubMed2007

Kinetic analysis of GTP hydrolysis catalysed by the Arf1-GTP-ASAP1 complex.

Arf (ADP-ribosylation factor) GAPs (GTPase-activating proteins) are enzymes that catalyse the hydrolysis of GTP bound to the small GTP-binding protein Arf. They have also been proposed to function as Arf effectors and oncogenes. We have set out to characterize the kinetics of the GAP-induced GTP hydrolysis using a truncated form of ASAP1 [Arf GAP with SH3 (Src homology 3) domain, ankyrin repeats and PH (pleckstrin homology) domains 1] as a model. We found that ASAP1 used Arf1-GTP as a substrate with a k(cat) of 57+/-5 s(-1) and a K(m) of 2.2+/-0.5 microM determined by steady-state kinetics and a kcat of 56+/-7 s(-1) determined by single-turnover kinetics. Tetrafluoroaluminate (AlF4-), which stabilizes complexes of other Ras family members with their cognate GAPs, also stabilized a complex of Arf1-GDP with ASAP1. As anticipated, mutation of Arg-497 to a lysine residue affected kcat to a much greater extent than K(m). Changing Trp-479, Iso-490, Arg-505, Leu-511 or Asp-512 was predicted, based on previous studies, to affect affinity for Arf1-GTP. Instead, these mutations primarily affected the k(cat). Mutants that lacked activity in vitro similarly lacked activity in an in vivo assay of ASAP1 function, the inhibition of dorsal ruffle formation. Our results support the conclusion that the Arf GAP ASAP1 functions in binary complex with Arf1-GTP to induce a transition state towards GTP hydrolysis. The results have led us to speculate that Arf1-GTP-ASAP1 undergoes a significant conformational change when transitioning from the ground to catalytically active state. The ramifications for the putative effector function of ASAP1 are discussed.

ADP-Ribosylation Factor 1↗

PubMed2006

Spontaneous patterning of confined granular rods.

Vertically vibrated rod-shaped granular materials confined to quasi-2D containers self-organize into distinct patterns. We find, consistent with theory and simulation, a density dependent isotropic-nematic transition. Along the walls, rods interact sterically to form a wetting layer. For high rod densities, complex patterns emerge as a result of competition between bulk and boundary alignment. A continuum elastic energy accounting for nematic distortion and local wall anchoring reproduces the structures seen experimentally.

Anisotropy↗

PubMed2005

Effect of rare events on out-of-equilibrium relaxation.

This Letter reports experimental and numerical results on particle dynamics in an out-of-equilibrium granular medium. We observed two distinct types of grain motion: the well known cage motion, during which a grain is always surrounded by the same neighbors, and low probability "jumps," during which a grain moves significantly more relative to the others. These observations are similar to the results obtained for other out-of-equilibrium systems (glasses, colloidal systems, etc.). Although such jumps are extremely rare, by inhibiting them in numerical simulations we demonstrate that they play a significant role in the relaxation of out-of-equilibrium systems.

Colloids↗

PubMed2005

Polymerization transitions in two-dimensional systems of dipolar spheres.

We investigate the self-organization of dipolar spheres into polymer chains as a fundamental model of the self-assembly of particles having anisotropic interparticle interactions. Our study involves a combination of modeling with vertically vibrated magnetic beads simulating a quasi-two-dimensional fluid at equilibrium and corresponding Monte Carlo simulations of hard spheres with embedded extended dipoles. We find a transition from a gas-like phase to a polymerized phase upon cooling, in accord with the analytic theory of equilibrium polymerization.

Colloids↗

PubMed2005

Chitosan-mediated and spatially selective electrodeposition of nanoscale particles.

Nanoscale particles offer a variety of interesting properties, and there is growing interest in their assembly into higher ordered structures. We report that the pH-responsive aminopolysaccharide chitosan can mediate the electrodeposition of model nanoparticles. Chitosan is known to electrodeposit at the cathode surface in response to a high localized pH. To demonstrate that chitosan can mediate nanoparticle deposition, we suspended fluorescently labeled latex nanoparticles (100 nm diameter spheres) in a chitosan solution (1%) and performed electrodeposition (0.05 mA/cm2 for several minutes). Results demonstrate that chitosan is required for nanoparticle electrodeposition; chitosan confers spatial selectivity to electrodeposition; and nanoparticles distribute throughout the electrodeposited chitosan film. Additionally, we observed that the deposited films reversibly swell upon rehydration. This work indicates that chitosan provides a simple means to assemble nanoparticles at addressable locations and provides further evidence that stimuli-responsive biological materials may facilitate fabrication at the microscale.

Biocompatible Materials↗

PubMed2004

Segregation in a monolayer of magnetic spheres.

Segregation and pattern formation is investigated for binary mixtures of granular magnetic spheres in a vertically vibrated monolayer. The spheres, all of equal mass and size, have a maximum surface magnetic field B induced by encased cylindrical magnetic cores of length l. For binary mixtures of particles with equal l but different B, we find that the particles spontaneously segregate when driven. For fixed vibration frequency, the segregation rate increases roughly linearly with driving acceleration over the amplitudes investigated. For systems of fixed particle number density, the rate of segregation also decreases as the volume fraction of "strong" (high B) particles increases. We find that segregation also occurs in binary mixtures of particles with equal B, but different l. Finally, using a simple model of spheres with dipolar and higher magnetic moments, we show that the observed segregation phenomena occur in conjunction with a decrease in magnetic energy.

Journal Article↗

PubMed2004

Transient and oscillatory granular shear flow.

The forces and particle motion during transient and oscillatory shear of granular material are investigated experimentally. In a shear cell of Taylor-Couette-type we find that how a granular shear flow starts depends strongly on the prior shear direction. If the shear direction is reversed, the material goes through a transient period during which the material compacts, the shear force is small, and the shear band is wide. Three-dimensional confocal imaging of particle rearrangements during shear reversal shows that bulk and surface flows are comparable. Repeated reversals, or oscillations of the shear direction, lead to additional compaction, which can be described by a stretched exponential, similar to compaction induced by tapping.

Anisotropy↗

PubMed2003

Superstable granular heap in a thin channel.

We observed experimentally a new regime for granular flows in an inclined channel with a flow-rate-controlled system. For high flow rates, the flow occurs atop a static granular heap whose angle is considerably higher than those usually exhibited by granular heaps. The properties of such superstable heaps (SSH) are drastically affected by a change in the channel width W. This indicates that the unusual stability of these heaps can be accounted for by the flowing layer and its friction on the sidewalls. A simple depth-averaged model, assuming Coulomb friction, shows that the SSH angle scales as h/W (W being the channel width), and that grain size plays no part.

Journal Article↗

PubMed2003

Pattern formation in a monolayer of magnetic spheres.

Pattern formation is investigated for a vertically vibrated monolayer of magnetic spheres. The spheres of diameter D encase cylindrical magnetic cores of length l. For large D/l, we find that the particles form a hexagonal-close-packed pattern in which the particles' dipole vectors assume a macroscopic circulating vortical pattern. For smaller D/l, the particles form concentric rings. The static configurational magnetic energy (which depends on D/l) appears to be a determining factor in pattern selection even though the experimental system is driven and dissipative.

Journal Article↗