Velocity oscillations in actin-based motility

We present a simple and generic theoretical description of actin-based motility, where polymerization of filaments maintains propulsion. The dynamics is driven by polymerization kinetics at the filaments' free ends, crosslinking of the actin network, attachment and detachment of filaments to the obstacle interfaces and entropic forces. We show that spontaneous oscillations in the velocity emerge in a broad range of parameter values, and compare our findings with experiments.Comment: 5 pages, 6 figure

Mechanical properties of branched actin filaments

Cells moving on a two dimensional substrate generate motion by polymerizing actin filament networks inside a flat membrane protrusion. New filaments are generated by branching off existing ones, giving rise to branched network structures. We investigate the force-extension relation of branched filaments, grafted on an elastic structure at one end and pushing with the free ends against the leading edge cell membrane. Single filaments are modeled as worm-like chains, whose thermal bending fluctuations are restricted by the leading edge cell membrane, resulting in an effective force. Branching can increase the stiffness considerably; however the effect depends on branch point position and filament orientation, being most pronounced for intermediate tilt angles and intermediate branch point positions. We describe filament networks without cross-linkers to focus on the effect of branching. We use randomly positioned branch points, as generated in the process of treadmilling, and orientation distributions as measured in lamellipodia. These networks reproduce both the weak and strong force response of lamellipodia as measured in force-velocity experiments. We compare properties of branched and unbranched networks. The ratio of the network average of the force per branched filament to the average force per unbranched filament depends on the orientation distribution of the filaments. The ratio exhibits compression dependence and may go up to about 4.5 in networks with a narrow orientation distribution. With orientation distributions measured in lamellipodia, it is about two and essentially independent from network compression, graft elasticity and filament persistence length

Discrete stochastic modeling of calcium channel dynamics

We propose a simple discrete stochastic model for calcium dynamics in living cells. Specifically, the calcium concentration distribution is assumed to give rise to a set of probabilities for the opening/closing of channels which release calcium thereby changing those probabilities. We study this model in one dimension, analytically in the mean-field limit of large number of channels per site N, and numerically for small N. As the number of channels per site is increased, the transition from a non-propagating region of activity to a propagating one changes in nature from one described by directed percolation to that of deterministic depinning in a spatially discrete system. Also, for a small number of channels a propagating calcium wave can leave behind a novel fluctuation-driven state, in a parameter range where the limiting deterministic model exhibits only single pulse propagation.Comment: 4 pages, 5 figures, submitted to PR

TeV Cherenkov Events as Bose-Einstein Gamma Condensations

The recent detection of gamma radiation from Mkn 501 at energies as high as 25 TeV suggests stringent upper bounds on the diffuse, far infrared, extragalactic radiation density. The production of electron-positron pairs through photon-photon collisions would prevent gamma photons of substantially higher energies from reaching us across distances of order 100 Mpc. However, coherently arriving TeV or sub-TeV gammas - Bose-Einstein condensations of photons at these energies - could mimic the Cherenkov shower signatures of extremely energetic gammas. To better understand such events, we describe their observational traits and discuss how they might be generated.Comment: 12 pages, 2 figures, accepted for publication in Ap.J.(Lett.

On the prospects of imaging Sagittarius A* from space

Very Long Baseline Interferometry (VLBI) at sub-millimeter waves has the potential to image the shadow of the black hole in the Galactic Center, Sagittarius A* (Sgr A*), and thereby test basic predictions of the theory of general relativity. We investigate the imaging prospects of a new Space VLBI mission concept. The setup consists of two satellites in polar or equatorial circular Medium-Earth Orbits with slightly different radii, resulting in a dense spiral-shaped uv-coverage with long baselines, allowing for extremely high-resolution and high-fidelity imaging of radio sources. We simulate observations of a general relativistic magnetohydrodynamics model of Sgr A* for this configuration with noise calculated from model system parameters. After gridding the $uv$-plane and averaging visibilities accumulated over multiple months of integration, images of Sgr A* with a resolution of up to 4 $\mu$as could be reconstructed, allowing for stronger tests of general relativity and accretion models than with ground-based VLBI.Comment: 4 pages, 4 figures, published in Proceedings IAU Symposium No. 342, 201

Interferometric observations of eta Carinae with VINCI/VLTI

Context: The bright star eta Carinae is the most massive and luminous star in our region of the Milky Way. Though it has been extensively studied using many different techniques, its physical nature and the mechanism that led to the creation of the Homunculus nebula are still debated. Aims: We aimed at resolving the central engine of the eta Carinae complex in the near-infrared on angular scales of a few milliarcseconds. Methods: We used the VINCI instrument of the VLTI to recombine coherently the light from two telescopes in the K band. Results: We report a total of 142 visibility measurements of eta Car, part of which were analyzed by Van Boekel et al. (2003). These observations were carried out on projected baselines ranging from 8 to 112 meters in length, using either two 0.35 m siderostats or two 8-meter Unit Telescopes. These observations cover the November 2001 - January 2004 period. Conclusions: The reported visibility data are in satisfactory agreement with the recent results obtained with AMBER/VLTI by Weigelt et al. (2006), asuming that the flux of eta Car encircled within 70 mas reaches 56% of the total flux within 1400 mas, in the K band. We also confirm that the squared visibility curve of eta Car as a function of spatial frequency follows closely an exponential model.Comment: Accepted for publication in A&A as a Research not

Modulated X-ray Emissivity near the Stress Edge in Sgr A*

Sgr A* is thought to be the radiative manifestation of a ~3.6E6 Msun supermassive black hole at the Galactic center. Its mm/sub-mm spectrum and its flare emission at IR and X-ray wavelengths may be produced within the inner ten Schwarzschild radii of a hot, magnetized Keplerian flow. The lightcurve produced in this region may exhibit quasi-periodic variability. We present ray-tracing simulations to determine the general-relativistically modulated X-ray luminosity expected from plasma coupled magnetically to the rest of the disk as it spirals inwards below the innermost stable circular orbit towards the "stress edge" in the case of a Schwarzschild metric. The resulting lightcurve exhibits a modulation similar to that observed during a recent X-ray flare from Sgr A*.Comment: 4 pages, 3 figures, accepted for publication in ApJ

Long‐term effects of Na+/Ca2+ exchanger inhibition with ORM‐11035 improves cardiac function and remodelling without lowering blood pressure in a model of heart failure with preserved ejection fraction

Aims: Heart failure with preserved ejection fraction (HFpEF) is increasingly common but there is currently no established pharmacological therapy. We hypothesized that ORM-11035, a novel specific Na+/Ca2+ exchanger (NCX) inhibitor, improves cardiac function and remodelling independent of effects on arterial blood pressure in a model of cardiorenal HFpEF. Methods and results: Rats were subjected to subtotal nephrectomy (NXT) or sham operation. Eight weeks after intervention, treatment for 16 weeks with ORM-11035 (1 mg/kg body weight) or vehicle was initiated. At 24 weeks, blood pressure measurements, echocardiography and pressure–volume loops were performed. Contractile function, Ca2+ transients and NCX-mediated Ca2+ extrusion were measured in isolated ventricular cardiomyocytes. NXT rats (untreated) showed a HFpEF phenotype with left ventricular (LV) hypertrophy, LV end-diastolic pressure (LVEDP) elevation, increased brain natriuretic peptide (BNP) levels, preserved ejection fraction and pulmonary congestion. In cardiomyocytes from untreated NXT rats, early relaxation was prolonged and NCX-mediated Ca2+ extrusion was decreased. Chronic treatment with ORM-11035 significantly reduced LV hypertrophy and cardiac remodelling without lowering systolic blood pressure. LVEDP [14 ± 3 vs. 9 ± 2 mmHg; NXT (n = 12) vs. NXT + ORM (n = 12); P = 0.0002] and BNP levels [71 ± 12 vs. 49 ± 11 pg/mL; NXT (n = 12) vs. NXT + ORM (n = 12); P < 0.0001] were reduced after ORM treatment. LV cardiomyocytes from ORM-treated rats showed improved active relaxation and diastolic cytosolic Ca2+ decay as well as restored NCX-mediated Ca2+ removal, indicating NCX modulation with ORM-11035 as a promising target in the treatment of HFpEF. Conclusion: Chronic inhibition of NCX with ORM-11035 significantly attenuated cardiac remodelling and diastolic dysfunction without lowering systemic blood pressure in this model of HFpEF. Therefore, long-term treatment with selective NCX inhibitors such as ORM-11035 should be evaluated further in the treatment of heart failure

Penetrating the Homunculus -- Near-Infrared Adaptive Optics Images of Eta Carinae

Near-infrared adaptive optics imaging with NICI and NaCO reveal what appears to be a three-winged or lobed pattern, the "butterfly nebula", outlined by bright Br$\gamma$ and H$_{2}$ emission and light scattered by dust. In contrast, the [Fe II] emission does not follow the outline of the wings, but shows an extended bipolar distribution which is tracing the Little Homunculus ejected in $\eta$ Car's second or lesser eruption in the 1890's. Proper motions measured from the combined NICI and NaCO images together with radial velocities show that the knots and filaments that define the bright rims of the butterfly were ejected at two different epochs corresponding approximately to the great eruption and the second eruption. Most of the material is spatially distributed 10\arcdeg to 20\arcdeg above and below the equatorial plane apparently behind the Little Homunculus and the larger SE lobe. The equatorial debris either has a wide opening angle or the clumps were ejected at different latitudes relative to the plane. The butterfly is not a coherent physical structure or equatorial torus but spatially separate clumps and filaments ejected at different times, and now 2000 to 4000 AU from the star.Comment: 42 pages, 12 figures, To appear in the Astronomical Journa

On the relation between filament density, force generation, and protrusion rate in mesenchymal cell motility

Lamellipodia are flat membrane protrusions formed during mesenchymal motion. Polymerization at the leading edge assembles the actin filament network and generates protrusion force. How this force is supported by the network and how the assembly rate is shared between protrusion and network retrograde flow determines the protrusion rate. We use mathematical modeling to understand experiments changing the F-actin density in lamellipodia of B16-F1 melanoma cells by modulation of Arp2/3 complex activity or knockout of the formins FMNL2 and FMNL3. Cells respond to a reduction of density with a decrease of protrusion velocity, an increase in the ratio of force to filament number, but constant network assembly rate. The relation between protrusion force and tension gradient in the F-actin network and the density dependency of friction, elasticity, and viscosity of the network explain the experimental observations. The formins act as filament nucleators and elongators with differential rates. Modulation of their activity suggests an effect on network assembly rate. Contrary to these expectations, the effect of changes in elongator composition is much weaker than the consequences of the density change. We conclude that the force acting on the leading edge membrane is the force required to drive F-actin network retrograde flow