Cooperative protein transport in cellular organelles

Compartmentalization into biochemically distinct organelles constantly exchanging material is one of the hallmarks of eukaryotic cells. In the most naive picture of inter-organelle transport driven by concentration gradients, concentration differences between organelles should relax. We determine the conditions under which cooperative transport, i.e. based on molecular recognition, allows for the existence and maintenance of distinct organelle identities. Cooperative transport is also shown to control the flux of material transiting through a compartmentalized system, dramatically increasing the transit time under high incoming flux. By including chemical processing of the transported species, we show that this property provides a strong functional advantage to a system responsible for protein maturation and sorting.Comment: 9 pages, 5 figure

An "All Possible Steps" Approach to the Accelerated Use of Gillespie's Algorithm

Many physical and biological processes are stochastic in nature. Computational models and simulations of such processes are a mathematical and computational challenge. The basic stochastic simulation algorithm was published by D. Gillespie about three decades ago [D.T. Gillespie, J. Phys. Chem. {\bf 81}, 2340, (1977)]. Since then, intensive work has been done to make the algorithm more efficient in terms of running time. All accelerated versions of the algorithm are aimed at minimizing the running time required to produce a stochastic trajectory in state space. In these simulations, a necessary condition for reliable statistics is averaging over a large number of simulations. In this study I present a new accelerating approach which does not alter the stochastic algorithm, but reduces the number of required runs. By analysis of collected data I demonstrate high precision levels with fewer simulations. Moreover, the suggested approach provides a good estimation of statistical error, which may serve as a tool for determining the number of required runs.Comment: Accepted for publication at the Journal of Chemical Physics. 19 pages, including 2 Tables and 4 Figure

Relaxation of finite perturbations: Beyond the Fluctuation-Response relation

We study the response of dynamical systems to finite amplitude perturbation. A generalized Fluctuation-Response relation is derived, which links the average relaxation toward equilibrium to the invariant measure of the system and points out the relevance of the amplitude of the initial perturbation. Numerical computations on systems with many characteristic times show the relevance of the above relation in realistic cases.Comment: 7 pages, 5 figure

Bistability of cell-matrix adhesions resulting from non-linear receptor-ligand dynamics

Bistability is a major mechanism for cellular decision making and usually results from positive feedback in biochemical control systems. Here we show theoretically that bistability between unbound and bound states of adhesion clusters results from positive feedback mediated by structural rather than biochemical processes, namely by receptor-ligand dissociation and association dynamics which depend non-linearly on mechanical force and receptor-ligand separation. For small cell-matrix adhesions, we find rapid switching between unbound and bound states, which in the initial stages of adhesion allows the cell to explore its environment through many transient adhesions.Comment: Revtex, 3 pages, 3 postscript figures included, to appear in Biophysical Journal as Biophysical Lette

Waiting time distribution for electron transport in a molecular junction with electron-vibration interaction

On the elementary level, electronic current consists of individual electron tunnelling events that are separated by random time intervals. The waiting time distribution is a probability to observe the electron transfer in the detector electrode at time $t+\tau$ given that an electron was detected in the same electrode at earlier time $t$. We study waiting time distribution for quantum transport in a vibrating molecular junction. By treating the electron-vibration interaction exactly and molecule-electrode coupling perturbatively, we obtain master equation and compute the distribution of waiting times for electron transport. The details of waiting time distributions are used to elucidate microscopic mechanism of electron transport and the role of electron-vibration interactions. We find that as nonequilibrium develops in molecular junction, the skewness and dispersion of the waiting time distribution experience stepwise drops with the increase of the electric current. These steps are associated with the excitations of vibrational states by tunnelling electrons. In the strong electron-vibration coupling regime, the dispersion decrease dominates over all other changes in the waiting time distribution as the molecular junction departs far away from the equilibrium

Sub-Poissonian atom number fluctuations by three-body loss in mesoscopic ensembles

We show that three-body loss of trapped atoms leads to sub-Poissonian atom number fluctuations. We prepare hundreds of dense ultracold ensembles in an array of magnetic microtraps which undergo rapid three-body decay. The shot-to-shot fluctuations of the number of atoms per trap are sub-Poissonian, for ensembles comprising 50--300 atoms. The measured relative variance or Fano factor $F=0.53\pm 0.22$ agrees very well with the prediction by an analytic theory ($F=3/5$) and numerical calculations. These results will facilitate studies of quantum information science with mesoscopic ensembles.Comment: 4 pages, 3 figure

Vlasov Equation In Magnetic Field

The linearized Vlasov equation for a plasma system in a uniform magnetic field and the corresponding linear Vlasov operator are studied. The spectrum and the corresponding eigenfunctions of the Vlasov operator are found. The spectrum of this operator consists of two parts: one is continuous and real; the other is discrete and complex. Interestingly, the real eigenvalues are infinitely degenerate, which causes difficulty solving this initial value problem by using the conventional eigenfunction expansion method. Finally, the Vlasov equation is solved by the resolvent method.Comment: 15 page

A quantitative comparison of sRNA-based and protein-based gene regulation

Small, non-coding RNAs (sRNAs) play important roles as genetic regulators in prokaryotes. sRNAs act post-transcriptionally via complementary pairing with target mRNAs to regulate protein expression. We use a quantitative approach to compare and contrast sRNAs with conventional transcription factors (TFs) to better understand the advantages of each form of regulation. In particular, we calculate the steady-state behavior, noise properties, frequency-dependent gain (amplification), and dynamical response to large input signals of both forms of regulation. While the mean steady-state behavior of sRNA-regulated proteins exhibits a distinctive tunable threshold-linear behavior, our analysis shows that transcriptional bursting leads to significantly higher intrinsic noise in sRNA-based regulation than in TF-based regulation in a large range of expression levels and limits the ability of sRNAs to perform quantitative signaling. Nonetheless, we find that sRNAs are better than TFs at filtering noise in input signals. Additionally, we find that sRNAs allow cells to respond rapidly to large changes in input signals. These features suggest a niche for sRNAs in allowing cells to transition quickly yet reliably between distinct states. This functional niche is consistent with the widespread appearance of sRNAs in stress-response and quasi-developmental networks in prokaryotes.Comment: 26 pages, 8 figures; accepted for publication in Molecular Systems Biolog

Fluctuation spectrum of quasispherical membranes with force-dipole activity

The fluctuation spectrum of a quasi-spherical vesicle with active membrane proteins is calculated. The activity of the proteins is modeled as the proteins pushing on their surroundings giving rise to non-local force distributions. Both the contributions from the thermal fluctuations of the active protein densities and the temporal noise in the individual active force distributions of the proteins are taken into account. The noise in the individual force distributions is found to become significant at short wavelengths.Comment: 9 pages, 2 figures, minor changes and addition