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At least 181 records · Page 10Linked to original sources
arXiv2012

Evidence for early identification of Alzheimer's disease

Alzheimer's disease is a human brain disease that affects a significant fraction of the population by causing problems with short-term memory, thinking, spatial orientation and behavior, memory loss and other intellectual abilities. Up to date there is no singular test that can definitively diagnose Alzheimer's disease, although imaging technology designed to detect Alzheimer's plaques and tangles is rapidly becoming more powerful and precise. In this paper we introduce a decision-making model, based on the combination of mitochondrial hypothesis-dynamics with the role of electromagnetic influences of the metal ions into the inner mitochondrial membrane and the quantitative analysis of mitochondrial population. While there are few disappointing clinical-trial results for drug treatments in patients with Alzheimer's disease, scientific community need alternative diagnostic tools rather investing mainly in amyloid-targeting drugs.

q-bio.NC↗
arXiv2012

Origin and diversification of a metabolic cycle in oligomer world

Based on the oligomer-world hypothesis we propose an abstract model where the molecular recognition among oligomers is described in the shape space. The origin of life in the oligomer world is regarded as the establishment of a metabolic cycle in a primitive cell. The cycle is sustained by the molecular recognition. If an original cell acquires the ability of the replication of oligomers, the relationship among oligomers changes due to the poor fidelity of the replication. This change leads to the diversification of metabolic cycles. The selection among diverse cycles is the basis of the evolution. The evolvability is one of the essential characters of life. We demonstrate the origin and diversification of the metabolic cycle by the computer simulation of our model. Such a simulation is expected to be the simplified demonstration of what actually occurred in the primordial soup. Our model describes an analog era preceding the digital era based on the genetic code.

q-bio.SC↗
arXiv2012

Extra-Low-Frequency Magnetic Fields alter Cancer Cells through Metabolic Restriction

Background: Biological effects of extra-low-frequency (ELF) magnetic fields (MF) have lacked a credible mechanism of interaction between MFs and living material. Objectives: Examine the effect of ELF-MFs on cancer cells. Methods: Five cancer cell lines were exposed to ELF-MFs within the range of 0.025 to 5 microT, and the cells were examined for karyotype changes after 6 days. Results: All cancer cells lines lost chromosomes from MF exposure, with a mostly flat dose-response. Constant MF exposures for three weeks allow a rising return to the baseline, unperturbed karyotypes. From this point, small MF increases or decreases are again capable of inducing karyotype contractions. Our data suggests that the karyotype contractions are caused by MF interference with mitochondria's ATP synthase (ATPS), compensated by the action of AMP-activated Protein Kinase (AMPK). The effects of MFs are similar to those of the ATPS inhibitor oligomycin. They are amplified by metformin, an AMPK stimulator, and attenuated by resistin, an AMPK inhibitor. Over environmental MFs, karyotype contractions of various cancer cell lines show exceptionally wide and flat dose-responses, except for those of erythro-leukemia cells, which display a progressive rise from 0.025 to 0.4 microT. Conclusions: The biological effects of MFs are connected to an alteration in the structure of water that impedes the flux of protons in ATPS channels. These results may be environmentally important, in view of the central roles played in human physiology by ATPS and AMPK, particularly in their links to diabetes, cancer and longevity.

physics.gen-ph↗
arXiv2012

Effect of voltage dynamics on response properties in a model of sensory hair cell

Sensory hair cells in auditory and vestibular organs rely on active mechanisms to achieve high sensitivity and frequency selectivity. Recent experimental studies have documented self-sustained oscillations in hair cells of lower vertebrates on two distinct levels. First, the hair bundle can undergo spontaneous mechanical oscillations. Second, somatic electric voltage oscillations across the baso-lateral membrane of the hair cell have been observed. We develop a biophysical model of the bullfrog's saccular hair cell consisting of two compartments, mechanical and electrical, to study how the mechanical and the voltage oscillations interact to produce coherent self-sustained oscillations and how this interaction contributes to the overall sensitivity and selectivity of the hair cell. The model incorporates nonlinear mechanical stochastic hair bundle system coupled bi-directionally to a Hodgkin-Huxley type system describing somatic ionic currents. We isolate regions of coherent spontaneous oscillations in the parameter space of the model and then study how coupling between compartments affect sensitivity of the hair cell to external mechanical perturbations. We show that spontaneous electrical oscillations may enhance significantly the sensitivity and selectivity of the hair cell.

physics.bio-ph↗
arXiv2012

Time in the cell: a plausible role for the plasma membrane

All cells must keep time to consistently perform vital biological functions. To that end, the coupling and interrelatedness of diverse subsecond events in the complex cellular environment, such as protein folding or translation rates, cannot simply result from the chance convergence of the inherent chemical properties of these phenomena, but may instead be synchronized through a cell-wide pacemaking mechanism. Picosecond vibrations of lipid membranes may play a role in such a mechanism.

q-bio.SC↗
arXiv2012

Flexibility Induced Motion Transition of Active Filament: Rotation without Long-range Hydrodynamic Interaction

We investigate the motion of active semiflexible filament with shape kinematics and hydrodynamic interaction including. Three types of filament motion are found: Translation, snaking and rotation. Change of flexibility will induce instability of shape kinematics and further result in asymmetry of shape kinematics respect to the motion of mass center, which are responsible to a continuous-like transition from translation to snaking and a first-order-like transition from snaking to rotation, respectively. Of particular interest, we find that long-range hydrodynamic interaction is not necessary for filament rotation, but can enhance remarkably the parameter region for its appearance. This finding may provide an evidence that the experimentally found collective rotation of active filaments is more likely to arise from the individual property even without the long-range hydrodynamic interaction.

cond-mat.soft↗
arXiv2012

Scale-dependent non-affine elasticity of semiflexible polymer networks

The cytoskeleton of eukaryotic cells provides mechanical support and governs intracellular transport. These functions rely on the complex mechanical properties of networks of semiflexible protein filaments. Recent theoretical interest has focused on mesoscopic properties of such networks and especially on the effect of local, non-affine bending deformations on mechanics. Here, we study the impact of local network deformations on the scale-dependent mobility of probe particles in entangled networks of semiflexible actin filaments by high-bandwidth microrheology. We find that micron-sized particles in these networks experience two opposing non-continuum elastic effects: entropic depletion reduces the effective network rigidity, while local non-affine deformations of the network substantially enhance the rigidity at low frequencies. We show that a simple model of lateral bending of filaments embedded in a viscoelastic background leads to a scaling regime for the apparent elastic modulus G'(ω) \sim ω^{9/16}, closely matching the experiments. These results provide quantitative evidence for how different a semiflexible polymer network can feel for small objects, and they demonstrate how non-affine bending deformations can be dominant for the mobility of vesicles and organelles in the cell.

cond-mat.soft↗
arXiv2012

A model for motor-mediated bidirectional transport along an antipolar microtubule bundle

Long-distance bidirectional transport of organelles depends on the motor proteins kinesin and dynein. Using quantitative data obtained from a fungal model system, we previously developed ASEP-models of bidirectional motion of motors along unipolar microtubules (MTs) near the cell ends of the elongated hyphal cells (herein referred as "unipolar section"). However, recent quantitative live cell imaging in this system has demonstrated that long-range motility of motors and their endosomal cargo mainly occurs along extended antipolar microtubule bundles within the central part of the cell (herein referred to as "bipolar section"). Dynein and kinesin-3 motors coordinate their activity to move early endosomes (EEs) in a bidirectional fashion, with dynein mediating retrograde motility along the unipolar section near the cell poles, whereas kinesin-3 is responsible for bidirectional motions along the antipolar section. Here we extend our modelling approach to simulate bidirectional motility along an antipolar microtubule bundle. In our model, cargos (particles) change direction on each MT with a turning rate $Ω$ and the MTs are linked to each other at the minus ends where particles can hop between MTs with a rate $q_1$ (obstacle-induced switching rate) or $q_2$ (end-induced switching rate). By numerical simulations and mean-field approximations, we investigate the distribution of particles along the MTs for different overall densities $Θ$. We find that even if $Θ$ is low, the system can exhibit shocks in the density profiles near plus and minus ends caused by queueing of particles. We also discuss how the switching rates $q_{1,2}$ influence the type of motor that dominates the active transport in the bundle.

cond-mat.stat-mech↗
arXiv2013

Sticky Surfaces: Sphere-Sphere Adhesion Dynamics

We present a multi-scale model to study the attachment of spherical particles with a rigid core, coated with binding ligands and in equilibrium with the surrounding, quiescent fluid medium. This class of fluid-immersed adhesion is widespread in many natural and engineering settings. Our theory highlights how the micro-scale binding kinetics of these ligands, as well as the attractive / repulsive surface potential in an ionic medium effects the eventual macro-scale size distribution of the particle aggregates (flocs). The results suggest that the presence of elastic ligands on the particle surface allow large floc aggregates by inducing efficient inter-floc collisions (i.e., a large, non-zero collision factor). Strong electrolytic composition of the surrounding fluid favors large floc formation as well.

physics.bio-ph↗
arXiv2013

Extremely low-frequency electromagnetic fields cause DNA strand breaks in normal Vero cells

Extremely low frequency electromagnetic fields aren't considered as a real carcinogenic agent despite the fact that some studies have showed impairment of the DNA integrity in different cells lines. The aim of this study was evaluation of the late effects of a 100 Hz and 5.6 mT electromagnetic field, applied continuously or discontinuously, on the DNA integrity of Vero cells assessed by alkaline Comet assay and by cell cycle analysis. Normal Vero cells were exposed to extremely low frequency electromagnetic fields (100 Hz, 5.6 mT) for 45 minutes. The Comet assay and cell cycle analysis were performed 48 hours after the treatment. Exposed samples presented an increase of the number of cells with high damaged DNA as compared with non-exposed cells. Quantitative evaluation of the comet assay showed a significantly ($<$0.001) increase of the tail lengths, of the quantity of DNA in tail and of Olive tail moments, respectively. The analysis of the registered comet indices showed that an extremely low frequency electromagnetic field of 100 Hz and 5.6 mT had a genotoxic impact on Vero cells. Cell cycle analysis showed an increase of the frequency of the cells in S phase, proving the occurrence of single strand breaks. The most probable mechanism of induction of the registered effects is the production of different types of reactive oxygen species.

q-bio.SC↗
arXiv2013

A theoretical model for attachment lifetimes of kinetochore-microtubules: Mechano-kinetic "catch-bond" mechanism for error-correction

Before cell division, two identical copies of chromosomes are pulled apart by microtubule (MT) filaments that approach the chromosomes from the opposite poles a mitotic spindle. Connection between the MTs and the chromosomes are mediated by a molecular complex called kinetochore. An externally applied tension can lead to detachment of the MTs from the kinetochore; the mean lifetime of such an attachment is essentially a mean first-passage time. In their in-vitro pioneering single-kinetochore experiments, Akiyoshi et al. (Nature 468, 576 (2010)), observed that the mean lifetimes of reconstituted MT-kinetochore attachments vary non-monotonically with increasing tension. The counter-intuitive stabilization of the attachments by small load forces was interpreted in terms of a catch-bond-like mechanism based on a phenomenological 2-state kinetic model. Here we develop the first detailed microscopic model for studying the dependence of the lifetime of the MT-kinetochore attachment on (a) the structure, (b) energetics, and (c) kinetics of the coupling. The catch-bond-like mechanism emerges naturally from this model. Moreover, in-silico experiments on this model reveal further interesting phenomena, arising from the subtle effects of competing sub-processes, which are likely to motivate new experiments in this emerging area of single-particle biophysics.

physics.bio-ph↗
arXiv2013

Nonlocal actin orientation models select for a unique orientation pattern

Many models have been developed to study the role of branching actin networks in motility. One important component of those models is the distribution of filament orientations relative to the cell membrane. Two mean-field models previously proposed are generalized and analyzed. In particular, we find that both models uniquely select for a dominant orientation pattern. In the linear case, the pattern is the eigenfunction associated with the principal eigenvalue. In the nonlinear case, we show there exists a unique equilibrium and that the equilibrium is locally stable. Approximate techniques are then used to provide evidence for global stability.

q-bio.SC↗
arXiv2013

The actin cortex as an active wetting layer

Using active gel theory we study theoretically the properties of the cortical actin layer of animal cells. The cortical layer is described as a non-equilibrium wetting film on the cell membrane. The actin density is approximately constant in the layer and jumps to zero at its edge. The layer thickness is determined by the ratio of the polymerization velocity and the depolymerization rate of actin.

cond-mat.soft↗
arXiv2013

Thermodynamic Relaxation Drives Expulsion in Giant Unilamellar Vesicles

We investigated the thermodynamic relaxation of giant unilamellar vesicles (GUVs) which contained small vesicles within their interior. Quenching these vesicles from their fluid phase (T>Tm) through the phase transition in the gel state (T<Tm) drives the inner vesicles to be expelled from the larger mother vesicle via the accompanying decrease in vesicle area by ~25% which forces a pore to open in the mother vesicle. We demonstrate that the proceeding time evolution of the resulting efflux follows the relaxation of the membrane area and describe the entire relaxation process using an Onsager-like nonequilibrium thermodynamics ansatz. As a consequence of the volume efflux internal vesicles are expelled from the mother vesicle. Although complete sealing of the pore may occur during the expulsion, the global relaxation dynamics is conserved. Finally, comparison of these results to morphological relaxation phenomena found in earlier studies reveals a universal relaxation behaviour in GUVs. When quenched from the fluid to gel phase the typical time scale of relaxation shows little variation and ranges between 4-5 seconds.

physics.bio-ph↗
arXiv2013

Phase Transition and dissipation driven budding in lipid vesicles

Membrane budding has been extensively studied as an equilibrium process attributed to the formation of coexisting domains or changes in the vesicle area to volume ratio (reduced volume). In contrast, non-equilibrium budding remains experimentally widely unexplored especially when time scales fall well below the characteristic diffusion time of lipidsτ . We show that localized mechanical perturbations, initiated by driving giant unilamellar vesicles (GUVs) through their lipid phase transition, leads to the immediate formation of rapidly growing, multiply localized, non-equilibrium buds, when the transition takes place at short timescales (<τ). We show that these buds arise from small fluid-like perturbations and grow as spherical caps in the third dimension, since in plane spreading is obstructed by the continuous rigid gel-like matrix. Accounting for both three and two dimensional viscosity, we demonstrate that dissipation decreases the size scale of the system and therefore favours the formation of multiple buds as long as the perturbation takes place above a certain critical rate. This rate depends on membrane and media viscosity and is qualitatively and quantitatively correctly predicted by our theoretical description.

physics.bio-ph↗
arXiv2013

Stochastic Modelling of T-Cell-Activation

We investigate a special part of the human immune system, namely the activation of T-Cells, using stochastic tools, especially sharp large deviation results. T-Cells have to distinguish reliably between foreign and self peptides which are both presented to them by antigen presenting cells. Our work is based on a model studied by Zint, Baake, and den Hollander, and originally proposed by van den Berg, Rand, and Burroughs. We are able to dispense with some restrictive distribution assumptions that were used previously, i.e. we establish a higher robustness of the model. A central issue is the analysis of two new perspectives to the scenario (two different quenched systems) in detail. This means that we do not only analyse the total probability of a T-Cell activation (the annealed case) but also consider the probability of an activation of one certain T-Cell type and the probability of a T-Cell activation by a certain antigen presenting cell (the quenched cases). Finally, we see analytically that the probability of T-Cell activation increases with the number of presented foreign peptides in all three cases.

math.PR↗
arXiv2013

Dependence of Substrate Irradiation Reaction Rate Stimulation on Lactic Dehydrogenase Source

Stimulation of LDH initial reaction rates by timed pre-irradiation of crystalline sodium pyruvate and lithium lactate is reported for enzymes isolated from rabbit muscle, pig heart, human erythrocytes and chicken heart. The phenomenon investigated is referred to as the Comorosan effect. For the mammalian source enzymes, the pyruvate irradiation stimulations occurred at irradiation times of 5 and 35 sec. and the lactate irradiation times at 15 and 45 seconds. In contrast, for the chicken heart enzyme, the pyruvate irradiation stimulations occurred at 15 and 35 sec., while those for lactate occurred at 5 and 20 sec. Thus, a shift in stimulatory irradiation times is found on going from the mammalian enzymes to the avian enzyme. A similar shift between mammalian and yeast enzymes has been established by Comorosan and co-workers. For the chicken heart LDH, the separation between successive irradiation times is different for the forward and reverse reactions. This is the first reported incidence of the separation not being the same.

q-bio.SC↗