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Herbert Levine

Publications and source records attributed to Herbert Levine.

At least 73 records · Page 4Linked to original sources

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↗

Activity-dependent stochastic resonance in recurrent neuronal networks

We use a biophysical model of a local neuronal circuit to study the implications of synaptic plasticity for the detection of weak sensory stimuli. Networks with fast plastic coupling show behavior consistent with stochastic resonance. Addition of an additional slow coupling that accounts for the asynchronous release of neurotransmitter results in qualitatively different properties of signal detection, and also leads to the appearance of transient post-stimulus bistability. Our results suggest testable hypothesis with regard to the self-organization and dynamics of local neuronal circuits.

q-bio.NC↗

Correlated Phenotypic Transitions to Competence in Bacterial Colonies

Genetic competence is a phenotypic state of a bacterial cell in which it is capable of importing DNA, presumably to hasten its exploration of alternate genes in its quest for survival under stress. Recently, it was proposed that this transition is uncorrelated among different cells in the colony. Motivated by several discovered signaling mechanisms which create colony-level responses, we present a model for the influence of quorum-sensing signals on a colony of B. Subtilis cells during the transition to genetic competence. Coupling to the external signal creates an effective inhibitory mechanism, which results in anti-correlation between the cycles of adjacent cells. We show that this scenario is consistent with the specific experimental measurement, which fails to detect some underlying collective signaling mechanisms. Rather, we suggest other parameters that should be used to verify the role of a quorum-sensing signal. We also study the conditions under which phenotypic spatial patterns may emerge.

q-bio.MN↗

microRNAs may sharpen spatial expression patterns

The precise layout of gene expression patterns is a crucial step in development. Formation of a sharp boundary between high and low expression domains requires a genetic mechanism which is both sensitive and robust to fluctuations, a demand that may not be easily achieved by morphogens alone. Recently it has been demonstrated that small RNAs (and, in particular, microRNAs) play many roles in embryonic development. While some RNAs are essential for embryogenesis, others are limited to fine-tuning a predetermined gene expression pattern. Here we explore the possibility that small RNAs participate in sharpening a gene expression profile that was crudely established by a morphogen. To this end we study a model where small RNAs interact with a target gene and diffusively move from cell to cell. Though diffusion generally smears spatial expression patterns, we find that intercellular mobility of small RNAs is actually critical in sharpening the interface between target expression domains in a robust manner. We discuss the applicability of our results, as examples, to the case of leaf polarity establishment in maize and Hox patterning in the early {\it Drosophila} embryo. Our findings point out the functional significance of some mechanistic properties, such as mobility of small RNAs and the irreversibility of their interactions. These properties are yet to be established directly for most classes of small RNAs. An indirect yet simple experimental test of the proposed mechanism is suggested in some detail.

q-bio.MN↗

The astrocyte as a gatekeeper of synaptic information transfer

We present a simple biophysical model for the coupling between synaptic transmission and the local calcium concentration on an enveloping astrocytic domain. This interaction enables the astrocyte to modulate the information flow from presynaptic to postsynaptic cells in a manner dependent on previous activity at this and other nearby synapses. Our model suggests a novel, testable hypothesis for the spike timing statistics measured for rapidly-firing cells in culture experiments.

q-bio.NC↗

Fluctuation Induced Instabilities in Front Propagation up a Co-Moving Reaction Gradient in Two Dimensions

We study 2D fronts propagating up a co-moving reaction rate gradient in finite number reaction-diffusion systems. We show that in a 2D rectangular channel, planar solutions to the deterministic mean-field equation are stable with respect to deviations from planarity. We argue that planar fronts in the corresponding stochastic system, on the other hand, are unstable if the channel width exceeds a critical value. Furthermore, the velocity of the stochastic fronts is shown to depend on the channel width in a simple and interesting way, in contrast to fronts in the deterministic MFE. Thus, fluctuations alter the behavior of these fronts in an essential way. These affects are shown to be partially captured by introducing a density cutoff in the reaction rate. Some of the predictions of the cutoff mean-field approach are shown to be in quantitative accord with the stochastic results.

cond-mat.stat-mech↗

Embryonic Pattern Scaling Achieved by Oppositely Directed Morphogen Gradients

Morphogens are proteins, often produced in a localised region, whose concentrations spatially demarcate regions of differing gene expression in developing embryos. The boundaries of expression must be set accurately and in proportion to the size of the one-dimensional developing field; this cannot be accomplished by a single gradient. Here, we show how a pair of morphogens produced at opposite ends of a developing field can solve the pattern-scaling problem. In the most promising scenario, the morphogens effectively interact according to the annihilation reaction $A+B\to\emptyset$ and the switch occurs according to the absolute concentration of $A$ or $B$. In this case embryonic markers across the entire developing field scale approximately with system size; this cannot be achieved with a pair of non-interacting gradients that combinatorially regulate downstream genes. This scaling occurs in a window of developing-field sizes centred at a few times the morphogen decay length.

q-bio.SC↗

Analytic approach to the evolutionary effects of genetic exchange

We present an approximate analytic study of our previously introduced model of evolution including the effects of genetic exchange. This model is motivated by the process of bacterial transformation. We solve for the velocity, the rate of increase of fitness, as a function of the fixed population size, $N$. We find the velocity increases with $\ln N$, eventually saturated at an $N$ which depends on the strength of the recombination process. The analytical treatment is seen to agree well with direct numerical simulations of our model equations.

q-bio.PE↗

Front Propagation up a Reaction Rate Gradient

We expand on a previous study of fronts in finite particle number reaction-diffusion systems in the presence of a reaction rate gradient in the direction of the front motion. We study the system via reaction-diffusion equations, using the expedient of a cutoff in the reaction rate below some critical density to capture the essential role of fl uctuations in the system. For large density, the velocity is large, which allows for an approximate analytic treatment. We derive an analytic approximation for the front velocity depe ndence on bulk particle density, showing that the velocity indeed diverge s in the infinite density limit. The form in which diffusion is impleme nted, namely nearest-neighbor hopping on a lattice, is seen to have an essential impact on the nature of the divergence.

cond-mat.stat-mech↗

Recombination dramatically speeds up evolution of finite populations

We study the role of recombination, as practiced by genetically-competent bacteria, in speeding up Darwinian evolution. This is done by adding a new process to a previously-studied Markov model of evolution on a smooth fitness landscape; this new process allows alleles to be exchanged with those in the surrounding medium. Our results, both numerical and analytic, indicate that for a wide range of intermediate population sizes, recombination dramatically speeds up the evolutionary advance.

q-bio.PE↗

Physical Schemata Underlying Biological Pattern Formation - Examples, Issues and Strategies

Biological systems excel at building spatial structures on scales ranging from nanometers to kilometers and exhibit temporal patterning from milliseconds to years. One approach that nature has taken to accomplish this relies on the harnessing of pattern-forming processes of non-equilibrium physics and chemistry. For these systems, the study of biological pattern formation starts with placing a biological phenomenon of interest within the context of the proper pattern-formation schema and then focusing on the ways in which control is exerted to adapt the pattern to the needs of the organism. This approach is illustrated by several examples, notably bacterial colonies (diffusive-growth schema) and intracellular calcium waves (excitable-media schema).

q-bio.CB↗

Fluctuation-regularized Front Propagation Dynamics

We introduce and study a new class of fronts in finite particle number reaction-diffusion systems, corresponding to propagating up a reaction rate gradient. We show that these systems have no traditional mean-field limit, as the nature of the long-time front solution in the stochastic process differs essentially from that obtained by solving the mean-field deterministic reaction-diffusion equations. Instead, one can incorporate some aspects of the fluctuations via introducing a density cutoff. Using this method, we derive analytic expressions for the front velocity dependence on bulk particle density and show self-consistently why this cutoff approach can get the correct leading-order physics.

cond-mat.stat-mech↗

Dynamic instabilities of fracture under biaxial strain using a phase field model

We present a phase field model of the propagation of fracture under plane strain. This model, based on simple physical considerations, is able to accurately reproduce the different behavior of cracks (the principle of local symmetry, the Griffith and Irwin criteria, and mode-I branching). In addition, we test our model against recent experimental findings showing the presence of oscillating cracks under bi-axial load. Our model again reproduces well observed supercritical Hopf bifurcation, and is therefore the first simulation which does so.

cond-mat.other↗

Phase field approach for modeling intracellular dynamics

We introduce a phase field approach for diffusion inside and outside a closed cell with damping and with source terms at the interface. The method is compared to exact solutions (where possible) and the more traditional finite element method. It is shown to be very accurate, easy to implement and computationally inexpensive. We apply our method to a recently introduced model for chemotaxis by Rappel et al. [Biophys. J. 83, 1361 (2002)].

cond-mat.stat-mech↗

Analytical study of the effect of recombination on evolution via DNA shuffling

We investigate a multi-locus evolutionary model which is based on the DNA shuffling protocol widely applied in \textit{in vitro} directed evolution. This model incorporates selection, recombination and point mutations. The simplicity of the model allows us to obtain a full analytical treatment of both its dynamical and equilibrium properties, for the case of an infinite population. We also briefly discuss finite population size corrections.

physics.bio-ph↗

Dynamics of Competitive Evolution on a Smooth Landscape

We study competitive DNA sequence evolution directed by {\it in vitro} protein binding. The steady-state dynamics of this process is well described by a shape-preserving pulse which decelerates and eventually reaches equilibrium. We explain this dynamical behavior within a continuum mean-field framework. Analytical results obtained on the motion of the pulse agree with simulations. Furthermore, finite population correction to the mean-field results are found to be insignificant.

cond-mat.stat-mech↗

Wave nucleation rate in excitable systems in the low noise limit

Motivated by recent experiments on intracellular calcium dynamics, we study the general issue of fluctuation-induced nucleation of waves in excitable media. We utilize a stochastic Fitzhugh-Nagumo model for this study, a spatially-extended non-potential pair of equations driven by thermal (i.e. white) noise. The nucleation rate is determined by finding the most probable escape path via minimization of an action related to the deviation of the fields from their deterministic trajectories. Our results pave the way both for studies of more realistic models of calcium dynamics as well as of nucleation phenomena in other non-equilibrium pattern-forming processes.

cond-mat↗

Does the continuum theory of dynamic fracture work?

We investigate the validity of the Linear Elastic Fracture Mechanics approach to dynamic fracture. We first test the predictions in a lattice simulation, using a formula of Eshelby for the time-dependent Stress Intensity Factor. Excellent agreement with the theory is found. We then use the same method to analyze the experiment of Sharon and Fineberg. The data here is not consistent with the theoretical expectation.

cond-mat.mtrl-sci↗