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At least 1,369 records · Page 76Linked to original sources

arXiv2007

Macroscopic consequences of calcium signaling in microdomains: A first passage time approach

Calcium (Ca) plays an important role in regulating various cellular processes. In a variety of cell types, Ca signaling occurs within microdomains where channels deliver localized pulses of Ca which activate a nearby collection of Ca-sensitive receptors. The small number of channels involved ensures that the signaling process is stochastic. The aggregate response of several thousand of these microdomains yields a whole-cell response which dictates the cell behavior. Here, we study analytically the statistical properties of a population of these microdomains in response to a trigger signal. We apply these results to understand the relationship between Ca influx and Ca release in cardiac cells. In this context, we use a first passage time approach to show analytically how Ca release in the whole cell depends on the single channel kinetics of Ca channels and the properties of microdomains. Using these results, we explain the underlying mechanism for the graded relationship between Ca influx and Ca release in cardiac cells.

q-bio.SC↗

arXiv2007

Cooperative action in eukaryotic gene regulation: physical properties of a viral example

The Epstein-Barr virus (EBV) infects more than 90% of the human population, and is the cause of several both serious and mild diseases. It is a tumorivirus, and has been widely studied as a model system for gene (de)regulation in human. A central feature of the EBV life cycle is its ability to persist in human B cells in states denoted latency I, II and III. In latency III the host cell is driven to cell proliferation and hence expansion of the viral population, but does not enter the lytic pathway, and no new virions are produced, while the latency I state is almost completely dormant. In this paper we study a physico-chemical model of the switch between latency I and latency III in EBV. We show that the unusually large number of binding sites of two competing transcription factors, one viral and one from the host, serves to make the switch sharper (higher Hill coefficient), either by cooperative binding between molecules of the same species when they bind, or by competition between the two species if there is sufficient steric hindrance.

q-bio.SC↗

arXiv2007

Forster mechanism of electron-driven proton pump

We examine a simple model of proton pumping through the inner membrane of mitochondria in the living cell. We demonstrate that the pumping process can be described using approaches of condensed matter physics. In the framework of this model, we show that the resonant Förster-type energy exchange due to electron-proton Coulomb interaction can provide an unidirectional flow of protons against an electrochemical proton gradient, thereby accomplishing proton pumping. The dependence of this effect on temperature as well as electron and proton voltage build-ups are obtained taking into account electrostatic forces and noise in the environment. We find that the proton pump works with maximum efficiency in the range of temperatures and transmembrane electrochemical potentials which correspond to the parameters of living cells.

cond-mat.mes-hall↗

arXiv2008

Quantifying intermittent transport in cell cytoplasm

Active cellular transport is a fundamental mechanism for protein and vesicle delivery, cell cycle and molecular degradation. Viruses can hijack the transport system and use it to reach the nucleus. Most transport processes consist of intermittent dynamics, where the motion of a particle, such as a virus, alternates between pure Brownian and directed movement along microtubules. In this communication, we estimate the mean time for particle to attach to a microtubule network. This computation leads to a coarse grained equation of the intermittent motion in radial and cylindrical geometries. Finally, by using the degradation activity inside the cytoplasm, we obtain refined asymptotic estimations for the probability and the mean time a virus reaches a small nuclear pore.

q-bio.QM↗

arXiv2008

Coexistence of amplitude and frequency modulations in intracellular calcium dynamics

The complex dynamics of intracellular calcium regulates cellular responses to information encoded in extracellular signals. Here, we study the encoding of these external signals in the context of the Li-Rinzel model. We show that by control of biophysical parameters the information can be encoded in amplitude modulation, frequency modulation or mixed (AM and FM) modulation. We briefly discuss the possible implications of this new role of information encoding for astrocytes.

q-bio.CB↗

arXiv2008

A model for hand-over-hand motion of molecular motors

A simple flashing ratchet model in two dimensions is proposed to simulate the hand-over-hand motion of two head molecular motors like kinesin. Extensive Langevin simulations of the model are performed. Good qualitative agreement with the expected behavior is observed. We discuss different regimes of motion and efficiency depending of model parameters.

physics.bio-ph↗

arXiv2007

Nanorheology of viscoelastic shells: Applications to viral capsids

We study the microrheology of nanoparticle shells [Dinsmore et al. Science 298, 1006 (2002)] and viral capsids [Ivanovska et al. PNAS 101, 7600 (2004)] by computing the mechanical response function and thermal fluctuation spectrum of a viscoelastic spherical shell that is permeable to the surrounding solvent. We determine analytically the damped dynamics of the shear, bend, and compression modes of the shell coupled to the solvent both inside and outside the sphere in the zero Reynolds number limit. We identify fundamental length and time scales in the system, and compute the thermal correlation function of displacements of antipodal points on the sphere and the mechanical response to pinching forces applied at these points. We describe how such a frequency-dependent antipodal correlation and/or response function, which should be measurable in new AFM-based microrheology experiments, can probe the viscoelasticity of these synthetic and biological shells constructed of nanoparticles.

cond-mat.soft↗

arXiv2008

Dynamic states of cells adhering in shear flow: from slipping to rolling

Motivated by rolling adhesion of white blood cells in the vasculature, we study how cells move in linear shear flow above a wall to which they can adhere via specific receptor-ligand bonds. Our computer simulations are based on a Langevin equation accounting for hydrodynamic interactions, thermal fluctuations and adhesive interactions. In contrast to earlier approaches, our model not only includes stochastic rules for the formation and rupture of bonds, but also fully resolves both receptor and ligand positions. We identify five different dynamic states of motion in regard to the translational and angular velocities of the cell. The transitions between the different states are mapped out in a dynamic state diagram as a function of the rates for bond formation and rupture. For example, as the cell starts to adhere under the action of bonds, its translational and angular velocities become synchronized and the dynamic state changes from slipping to rolling. We also investigate the effect of non-molecular parameters. In particular, we find that an increase in viscosity of the medium leads to a characteristic expansion of the region of stable rolling to the expense of the region of firm adhesion, but not to the expense of the regions of free or transient motion. Our results can be used in an inverse approach to determine single bond parameters from flow chamber data on rolling adhesion.

q-bio.CB↗

arXiv2008

Traffic of single-headed motor proteins KIF1A: effects of lane changing

KIF1A kinesins are single-headed motor proteins which move on cylindrical nano-tubes called microtubules (MT). A normal MT consists of 13 protofilaments on which the equispaced motor binding sites form a periodic array. The collective movement of the kinesins on a MT is, therefore, analogous to vehicular traffic on multi-lane highways where each protofilament is the analogue of a single lane. Does lane-changing increase or decrease the motor flux per lane? We address this fundamental question here by appropriately extending a recent model [{\it Phys. Rev. E {\bf 75}, 041905 (2007)}]. By carrying out analytical calculations and computer simulations of this extended model, we predict that the flux per lane can increase or decrease with the increasing rate of lane changing, depending on the concentrations of motors and the rate of hydrolysis of ATP, the ``fuel'' molecules. Our predictions can be tested, in principle, by carrying out {\it in-vitro} experiments with fluorescently labelled KIF1A molecules.

physics.bio-ph↗

arXiv2008

Proton transport and torque generation in rotary biomotors

We analyze the dynamics of rotary biomotors within a simple nano-electromechanical model, consisting of a stator part and a ring-shaped rotor having twelve proton-binding sites. This model is closely related to the membrane-embedded F$_0$ motor of adenosine triphosphate (ATP) synthase, which converts the energy of the transmembrane electrochemical gradient of protons into mechanical motion of the rotor. It is shown that the Coulomb coupling between the negative charge of the empty rotor site and the positive stator charge, located near the periplasmic proton-conducting channel (proton source), plays a dominant role in the torque-generating process. When approaching the source outlet, the rotor site has a proton energy level higher than the energy level of the site, located near the cytoplasmic channel (proton drain). In the first stage of this torque-generating process, the energy of the electrochemical potential is converted into potential energy of the proton-binding sites on the rotor. Afterwards, the tangential component of the Coulomb force produces a mechanical torque. We demonstrate that, at low temperatures, the loaded motor works in the shuttling regime where the energy of the electrochemical potential is consumed without producing any unidirectional rotation. The motor switches to the torque-generating regime at high temperatures, when the Brownian ratchet mechanism turns on. In the presence of a significant external torque, created by ATP hydrolysis, the system operates as a proton pump, which translocates protons against the transmembrane potential gradient. Here we focus on the F$_0$ motor, even though our analysis is applicable to the bacterial flagellar motor.

cond-mat.other↗

arXiv2008

Theory of DNA translocation through narrow ion channels and nanopores with charged walls

Translocation of a single stranded DNA through genetically engineered $α$-hemolysin channels with positively charged walls is studied. It is predicted that transport properties of such channels are dramatically different from neutral wild type $α$-hemolysin channel. We assume that the wall charges compensate the fraction $x$ of the bare charge $q_{b}$ of the DNA piece residing in the channel. Our prediction are as follows (i) At small concentration of salt the blocked ion current decreases with $x$. (ii) The effective charge $q$ of DNA piece, which is very small at $x = 0$ (neutral channel) grows with $x$ and at $x=1$ reaches $q_{b}$. (iii) The rate of DNA capture by the channel exponentially grows with $x$. Our theory is also applicable to translocation of a double stranded DNA in narrow solid state nanopores with positively charged walls.

q-bio.SC↗

arXiv2008

Effects of the chemomechanical stepping cycle on the traffic of molecular motors

We discuss effects of the stepping kinetics of molecular motors on their traffic behavior on crowded filaments using a simple two-state chemomechanical cycle. While the general traffic behavior is quite robust with respect to the detailed kinetics of the step, a few observable parameters exhibit a strong dependence on these parameters. Most strikingly, the effective unbinding rate of the motors may both increase and decrease with increasing traffic density, depending on the details of the motor step. Likewise the run length either exhibits a strong decrease or almost no dependence on the traffic density. We compare our theoretical results with recent experimental observations on motor traffic.

cond-mat.stat-mech↗

arXiv2008

A model of HIV budding and self-assembly, role of cell membrane

Budding from the plasma membrane of the host cell is an indispensable step in the life cycle of the Human Immunodeficiency Virus (HIV), which belongs to a large family of enveloped RNA viruses, retroviruses. Unlike regular enveloped viruses, retrovirus budding happens {\em concurrently} with the self-assembly of retrovirus protein subunits (Gags) into spherical virus capsids on the cell membrane. Led by this unique budding and assembly mechanism, we study the free energy profile of retrovirus budding, taking into account of the Gag-Gag attraction energy and the membrane elastic energy. We find that if the Gag-Gag attraction is strong, budding always proceeds to completion. During early stage of budding, the zenith angle of partial budded capsids, $α$, increases with time as $α\propto t^{1/3}$. However, when Gag-Gag attraction is weak, a metastable state of partial budding appears. The zenith angle of these partially spherical capsids is given by $α_0\simeq(τ^2/κσ)^{1/4}$ in a linear approximation, where $κ$ and $σ$ are the bending modulus and the surface tension of the membrane, and $τ$ is a line tension of the capsid proportional to the strength of Gag-Gag attraction. Numerically, we find $α_0<0.3π$ without any approximations. Using experimental parameters, we show that HIV budding and assembly always proceed to completion in normal biological conditions. On the other hand, by changing Gag-Gag interaction strength or membrane rigidity, it is relatively easy to tune it back and forth between complete budding and partial budding. Our model agrees reasonably well with experiments observing partial budding of retroviruses including HIV.

q-bio.SC↗

arXiv2008

Detection of subthreshold pulses in neurons with channel noise

Neurons are subject to various kinds of noise. In addition to synaptic noise, the stochastic opening and closing of ion channels represents an intrinsic source of noise that affects the signal processing properties of the neuron. In this paper, we studied the response of a stochastic Hodgkin-Huxley neuron to transient input subthreshold pulses. It was found that the average response time decreases but variance increases as the amplitude of channel noise increases. In the case of single pulse detection, we show that channel noise enables one neuron to detect the subthreshold signals and an optimal membrane area (or channel noise intensity) exists for a single neuron to achieve optimal performance. However, the detection ability of a single neuron is limited by large errors. Here, we test a simple neuronal network that can enhance the pulse detecting abilities of neurons and find dozens of neurons can perfectly detect subthreshold pulses. The phenomenon of intrinsic stochastic resonance is also found both at the level of single neurons and at the level of networks. At the network level, the detection ability of networks can be optimized for the number of neurons comprising the network.

q-bio.NC↗

arXiv2008

A three-state kinetic mechanism for scaffold mediated signal transduction

Signaling events in eukaryotic cells are often guided by a scaffolding protein. Scaffold proteins assemble multiple proteins in a spatially localized signaling complex and exert numerous physical effects on signaling pathways. To study these effects, we consider a minimal, three-state kinetic model of scaffold mediated kinase activation. We first introduce and apply a path summation technique to obtain approximate solutions to a single molecule master equation that governs protein kinase activation. We then consider exact numerical solutions. We comment on when this approximation is appropriate and then use this analysis to illustrate the competition of processes occurring at many time scales involved in signal transduction in the presence of a scaffold protein. The findings are consistent with recent experiments and simulation data. Our results provide a framework and offer a mechanism for understanding how scaffold proteins can influence the shape of the waiting time distribution of kinase activation and effectively broaden the times over which protein kinases are activated in the course of cell signaling.

q-bio.SC↗

arXiv2008

Fluctuations in protein synthesis from a single RNA template: stochastic kinetics of ribosomes

Proteins are polymerized by cyclic machines called ribosome which use their messenger RNA (mRNA) track also as the corresponding template and the process is called translation. We explore, in depth and detail, the stochastic nature of the translation. We compute various distributions associated with the translation process; one of them, namely dwell time distribution, has been measured in recent single ribosome experiments (Wen et al. Nature {\bf 452}, 598 (2008)). The form of this distribution predicted by our theory is consistent with that extracted from the experimental data. For our quantitative calculations, we use a model that captures both the mechano-chemistry of each individual ribosome as well as their steric interactions. We also demonstrate the effects of the sequence inhomogeneities of real genes on the fluctuations and noise in translation. In principle, our new predictions can be tested by carrying out {\it in-vitro} experiments.

physics.bio-ph↗

arXiv2008

Stochastic model for nucleosome sliding in the presence of DNA ligands

Heat-induced mobility of nucleosomes along DNA is an experimentally well-studied phenomenon. A recent experiment shows that the repositioning is modified in the presence of minor-groove binding DNA ligands. We present here a stochastic three-state model for the diffusion of a nucleosome along DNA in the presence of such ligands. It allows us to describe the dynamics and the steady state of such a motion analytically. The analytical results are in excellent agreement with numerical simulations of this stochastic process.With this model, we study the response of a nucleosome to an external force and how it is affected by the presence of ligands.

cond-mat.soft↗

arXiv2007

Diffusion, dimensionality and noise in transcriptional regulation

The precision of biochemical signaling is limited by randomness in the diffusive arrival of molecules at their targets. For proteins binding to the specific sites on the DNA and regulating transcription, the ability of the proteins to diffuse in one dimension by sliding along the length of the DNA, in addition to their diffusion in bulk solution, would seem to generate a larger target for DNA binding, consequently reducing the noise in the occupancy of the regulatory site. Here we show that this effect is largely cancelled by the enhanced temporal correlations in one dimensional diffusion. With realistic parameters, sliding along DNA has surprisingly little effect on the physical limits to the precision of transcriptional regulation.

q-bio.MN↗