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At least 235 records · Page 13Linked to original sources

arXiv2014

Influence of Multiplicative Stochastic Variation on Translational Elongation Rates

Recent experiments have shown that stochastic effects exerted at the level of translation contribute a substantial portion of the variation in abundance of proteins expressed at moderate to high levels. This study analyzes translational noise arising from fluctuations in residue-specific elongation rates. The resulting variation has multiplicative components that lead individual protein abundances in a population to exhibit approximately log-normal behavior. The high variability inherent in the process leads to parameter variation that has the features of a type of noise in biological systems that has been characterized as extrinsic. Elongation rate variation offers an accounting for a major component of extrinsic noise, and the analysis provided here highlights a probability distribution that is a natural extension of the Poisson and has broad applicability to many types of multiplicative noise processes.

q-bio.SC↗

arXiv2014

Sensitivity of mRNA Translation

Using the dynamic mean-field approximation of the totally asymmetric simple exclusion process (TASEP), we investigate the effect of small changes in the initiation, exit, and elongation rates along the mRNA strand on the steady state protein translation rate. We focus on two special cases where exact closed-form expressions for the translation rate sensitivity can be derived. We discuss the ramifications of our results in the context of functional genomics, molecular evolution, and synthetic biology.

q-bio.GN↗

arXiv2014

Salinity tolerance in plants: attempts to manipulate ion transport

Ion transport is the major determining factor of salinity tolerance in plants. A simple scheme of a plant cell with ion fluxes provides basic understanding of ion transport and the corresponding changes of ion concentrations under salinity. The review describes in detail basic principles of ion transport for a plant cell, introduces set of transporters essential for sodium and potassium uptake and efflux, analyses driving forces of ion transport and compares ion fluxes measured by several techniques. Study of differences in ion transport between salt tolerant halophytes and salt-sensitive plants with an emphasis on transport of potassium and sodium via plasma membranes offers knowledge for increasing salinity tolerance. Effects of salt stress on ion transport properties of membranes show huge opportunities for manipulating ion transport. Several attempts to overexpress or knockout ion transporters for changing salinity tolerance are described. Future perspectives are questioned with more attention given to potential candidate ion channels and transporters for altered expression. The potential direction of increasing salinity tolerance by modifying ion channels and transporters is discussed and questioned. An alternative approach from synthetic biology is to modify the existing membrane transport proteins or create new ones with desired properties for transforming agricultural crops. The approach had not been widely used earlier and leads also to theoretical and pure scientific aspects of protein chemistry, structure-function relations of membrane proteins, systems biology and physiology of stress and ion homeostasis.

q-bio.SC↗

arXiv2014

Connecting local active forces to macroscopic stress in elastic media

In contrast with ordinary materials, living matter drives its own motion by generating active, out-of-equilibrium internal stresses. These stresses typically originate from localized active elements embedded in an elastic medium, such as molecular motors inside the cell or contractile cells in a tissue. While many large-scale phenomenological theories of such active media have been developed, a systematic understanding of the emergence of stress from the local force-generating elements is lacking. In this paper, we present a rigorous theoretical framework to study this relationship. We show that the medium's macroscopic active stress tensor is equal to the active elements' force dipole tensor per unit volume in both continuum and discrete linear homogeneous media of arbitrary geometries. This relationship is conserved on average in the presence of disorder, but can be violated in nonlinear elastic media. Such effects can lead to either a reinforcement or an attenuation of the active stresses, giving us a glimpse of the ways in which nature might harness microscopic forces to create active materials.

cond-mat.soft↗

arXiv2014

Quantifying the role of chaperones in protein translocation by computational modelling

The molecular chaperone Hsp70 plays a central role in the import of cytoplasmic proteins into organelles, driving their translocation by binding them from the organellar interior. Starting from the experimentally-determined structure of the \textit{E. coli} Hsp70, we computed, by means of molecular simulations, the effective free-energy profile for substrate translocation upon chaperone binding. We then used the resulting free energy to quantitatively characterize the kinetics of the import process, whose comparison with unassisted translocation highlights the essential role played by Hsp70 in importing cytoplasmic proteins.

q-bio.SC↗

arXiv2014

Efficiency of cellular uptake of nanoparticles via receptor-mediated endocytosis

Experiments show that cellular uptake of nanoparticles, via receptor-mediated endocytosis, strongly depends on nanoparticle size. There is an optimal size, approximately 50 nm in diameter, at which cellular uptake is the highest. In addition, there is a maximum size, approximately 200 nm, beyond which uptake via receptor-mediated endocytosis does not occur. By comparing results from different experiments, we found that these sizes weakly depend on the type of cells, nanoparticles, and ligands used in the experiments. Here, we argue that these observations are consequences of the energetics and assembly dynamics of the protein coat that forms on the cytoplasmic side of the outer cell membrane during receptor-mediated endocytosis. Specifically, we show that the energetics of coat formation imposes an upper bound on the size of the nanoparticles that can be internalized, whereas the nanoparticle-size-dependent dynamics of coat assembly results in the optimal nanoparticle size. The weak dependence of the optimal and maximum sizes on cell-nanoparticle-ligand type also follows naturally from our analysis.

q-bio.SC↗

arXiv2014

Theory of cargo and membrane trafficking

Endocytosis underlies many cellular functions including signaling and nutrient uptake. The endocytosed cargo gets redistributed across a dynamic network of endosomes undergoing fusion and fission. Here, a theoretical approach is reviewed which can explain how the microscopic properties of endosome interactions cause the emergent macroscopic properties of cargo trafficking in the endosomal network. Predictions by the theory have been tested experimentally and include the inference of dependencies and parameter values of the microscopic processes. This theory could also be used to infer mechanisms of signal-trafficking crosstalk. It is applicable to in vivo systems since fixed samples at few time points suffice as input data.

q-bio.SC↗

arXiv2014

Single-enzyme kinetics with branched pathways: exact theory and series expansion

The progress of the successive rounds of catalytic conversion of substrates into product(s) by a single enzyme is characterized by the distribution of turnover times. Establishing the most general form of dependence of this distribution on the substrate concentration [S] is one of the fundamental challenges in single molecule enzymology. The distribution of the times of dwell of a molecular motor at the successive positions on its track is an analogous quantity. We derive approximate series expansions for the [ATP]-dependence of the first two moments of the dwell time distributions of motors that catalyze hydrolysis of ATP to draw input energy. Comparison between our results for motors with branched pathways and the corresponding expressions reported earlier for linear enzymatic pathways provides deep insight into the effects of the branches. Such insight is likely to help in discovering the most general form of [S]-dependence of these fundamental distributions.

physics.chem-ph↗

arXiv2015

Effects of aging in catastrophe on the steady state and dynamics of a microtubule population

Several independent observations have suggested that catastrophe transition in microtubules is not a first-order process, as is usually assumed. Recent {\it in vitro} observations by Gardner et al.[ M. K. Gardner et al., Cell {\bf147}, 1092 (2011)] showed that microtubule catastrophe takes place via multiple steps and the frequency increases with the age of the filament. Here, we investigate, via numerical simulations and mathematical calculations, some of the consequences of age dependence of catastrophe on the dynamics of microtubules as a function of the aging rate, for two different models of aging: exponential growth, but saturating asymptotically and purely linear growth. The boundary demarcating the steady state and non-steady state regimes in the dynamics is derived analytically in both cases. Numerical simulations, supported by analytical calculations in the linear model, show that aging leads to non-exponential length distributions in steady state. More importantly, oscillations ensue in microtubule length and velocity. The regularity of oscillations, as characterized by the negative dip in the autocorrelation function, is reduced by increasing the frequency of rescue events. Our study shows that age dependence of catastrophe could function as an intrinsic mechanism to generate oscillatory dynamics in a microtubule population, distinct from hitherto identified ones.

q-bio.SC↗

arXiv2014

Asymptotic and numerical methods for metastable events in stochastic gene networks

A general class of stochastic gene expression models with self regulation is considered. One or more genes randomly switch between regulatory states, each having a different mRNA transcription rate. The gene or genes are self regulating when the proteins they produce affect the rate of switching between regulatory states. Under weak noise conditions, the deterministic forces are much stronger than fluctuations from gene switching and protein synthesis. Metastable transitions, such as bistable switching, can occur under weak noise conditions, causing dramatic shifts in the expression of a gene. A general tool used to describe metastability is the quasi stationary analysis (QSA). A large deviation principle is derived so that the QSA can explicitly account for random gene switching without using an adiabatic limit or diffusion approximation, which are unreliable and inaccurate for metastable events.This allows the existing asymptotic and numerical methods that have been developed for continuous Markov processes to be used to analyze the full model.

q-bio.MN↗

arXiv2015

New insights on the Dynamic Cellular Metabolism

A large number of studies have shown the existence of metabolic covalent modifications in different molecular structures, able to store biochemical information that is not encoded by the DNA. Some of these covalent mark patterns can be transmitted across generations (epigenetic changes). Recently, the emergence of Hopfield-like attractor dynamics has been observed in the self-organized enzymatic networks, which have the capacity to store functional catalytic patterns that can be correctly recovered by the specific input stimuli. The Hopfield-like metabolic dynamics are stable and can be maintained as a long-term biochemical memory. In addition, specific molecular information can be transferred from the functional dynamics of the metabolic networks to the enzymatic activity involved in the covalent post-translational modulation so that determined functional memory can be embedded in multiple stable molecular marks. Both the metabolic dynamics governed by Hopfield-type attractors (functional processes) and the enzymatic covalent modifications of determined molecules (structural dynamic processes) seem to represent the two stages of the dynamical memory of cellular metabolism (metabolic memory). Epigenetic processes appear to be the structural manifestation of this cellular metabolic memory. Here, a new framework for molecular information storage in the cell is presented, which is characterized by two functionally and molecularly interrelated systems: a dynamic, flexible and adaptive system (metabolic memory) and an essentially conservative system (genetic memory). The molecular information of both systems seems to coordinate the physiological development of the whole cell.

q-bio.SC↗

arXiv2015

Persistence of activity in noisy motor-filament assemblies

Long, elastic filaments cross-linked and deformed by active molecular motors occur in various natural settings. The overall macroscopic mechanical response of such a composite network depends on the coupling between the active and the passive properties of the underlying constituents and nonlocal interactions between different parts of the composite. In a simple one dimensional system, using a mean field model, it has been shown that the combination of motor activity and finite filament extensibility yields a persistence length scale over which strain decays. Here we study a similar system, in the complementary limit of strong noise and moderate extensibility, using Brownian multi-particle collision dynamics-based numerical simulations that includes the coupling between motor kinetics and local filament extensibility. While the numerical model shows deviations from the mean field predictions due to the presence of strong active noise caused by the variations in individual motor activity, several qualitative features are still retained. Specifically, for fixed motor attachment and detachment rates, the decay is length is set by the ratio of the passive elasticity to the active shear resistance generated by attached motors. Our study generalizes the notion of persistence in passive thermal systems to actively driven systems with testable predictions.

physics.bio-ph↗

arXiv2018

Persistence of strain in motor-filament assemblies

Crosslinked semi-flexible and flexible filaments that are actively deformed by molecular motors occur in various natural settings, such as the ordered eukaryotic flagellum, and the disordered cytoskeleton. The deformation of these composite systems is driven by active motor forces and resisted by passive filament elasticity, and structural constraints due to permanent cross-links. Using a mean field theory for a one-dimensional ordered system, we show that the combination of motor activity and finite filament extensibility yields a characteristic persistence length scale over which active strain decays. This decay length is set by the ability of motors to respond to combination of the weak extensional elasticity, passive shear resistance and the viscoelastic properties of the motor assembly, and generalizes the notion of persistence in purely thermal filaments to active systems.

physics.bio-ph↗

arXiv2015

Signal focusing through active transport

In biological cells and novel diagnostic devices biochemical receptors need to be sensitive to extremely small concentration changes of signaling molecules. The accuracy of such molecular signaling is ultimately limited by the counting noise imposed by the thermal diffusion of molecules. Many macromolecules and organelles transiently bind to molecular motors and are then actively transported. We here show that a random albeit directed delivery of signaling molecules to within a typical diffusion distance to the receptor reduces the correlation time of the counting noise, effecting an improved sensing precision. The conditions for this active focusing are indeed compatible with observations in living cells. Our results are relevant for a better understanding of molecular cellular signaling and the design of novel diagnostic devices.

q-bio.SC↗

arXiv2015

Cryoelectron Microscopy as a Functional Instrument for Systems Biology, Structural Analysis & Experimental Manipulations with Living Cells. A comprehensive review of the current works

The aim of this paper is to give an introductory review of the cryoelectron microscopy as a complex data source for the most of the system biology branches, including the most perspective non-local approaches known as "localomics" and "dynamomics". A brief summary of various cryoelectron mi-croscopy methods and corresponding system biological ap-proaches is given in the text. The above classification can be considered as a useful framework for the primary comprehen-sions about cryoelectron microscopy aims and instrumental tools. We do not discuss any of these concepts in details, but merely point out that their methodological complexity follows only from the structure-functional complexity of biological systems which are investigated in this manner. We also postu-late that one can employ some of the cryoelectron microscopic techniques not only for observation, but also for modification and structural refunctionalization of some biological and similar soft matter objects and microscopic samples. In other worlds, we start with the cryoelectron microscopy as a tool for the sys-tem biology and progress to its applying as an instrument for system biology and functional biomimetics; i.e. "system cryobi-ology" goes over into "synthetic cryobiology" or "cryogenic biomimetics". All these conclusions can be deduced from the most recent works of the latest years, including just submitted foreign papers. This article provides an up-to-date description of the conceptual basis for the novel view on the computational cryoelectron microscopy (in silico) approaches and the data mining principles which lie at the very foundation of modern structural analysis and reconstruction.

q-bio.SC↗

arXiv2016

An introduction to linear stability analysis for deciphering spatial patterns in signaling networks

Mathematical modeling is now used commonly in the analysis of signaling networks. With advances in high resolution microscopy, the spatial location of different signaling molecules and the spatio-temporal dynamics of signaling microdomains are now widely acknowledged as key features of biochemical signal transduction. Reaction-diffusion mechanisms are commonly used to model such features, often with a heavy reliance on numerical simulations to obtain results. However, simulations are parameter dependent and may not be able to provide an understanding of the full range of the system responses. Analytical approaches on the other hand provide a framework to study the entire phase space. In this tutorial, we provide a largely analytical method for studying reaction-diffusion models and analyzing their stability properties. Using two representative biological examples, we demonstrate how this approach can guide experimental design.

q-bio.SC↗

arXiv2015

Analysis of single particle trajectories: when things go wrong

To recover the long-time behavior and the statistics of molecular trajectories from the large number (tens of thousands) of their short fragments, obtained by super-resolution methods at the single molecule level, data analysis based on a stochastic model of their non-equilibrium motion is required. Recently, we characterized the local biophysical properties underlying receptor motion based on coarse-grained long-range interactions, corresponding to attracting potential wells of large sizes. The purpose of this letter is to discuss optimal estimators and show what happens when thing goes wrong.

physics.bio-ph↗

arXiv2015

Epigenetics: What it is about?

Epigenetics has captured the attention of scientists in the past decades, yet its scope has been continuously changing. In this paper, we give an overview on how and why its definition has evolved and suggest several clarification on the concepts used in this field, in particular, on the notions of epigenetic information, epigenetic stability and epigenetic templating. Another issue that we address is the role of epigenetic information. Not only it is important in allowing alternative interpretations of genetic information, but it appears to be important in protecting the genetic information, moreover, we suggest that this function appeared first in evolution and only later on the epigenetic mechanisms were recruited to play a role in cell differentiation.

q-bio.SC↗