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arXiv2013

Spatial population expansion promotes the evolution of cooperation in an experimental Prisoner's Dilemma

Cooperation is ubiquitous in nature, but explaining its existence remains a central interdisciplinary challenge. Cooperation is most difficult to explain in the Prisoner's Dilemma game, where cooperators always lose in direct competition with defectors despite increasing mean fitness. Here we demonstrate how spatial population expansion, a widespread natural phenomenon, promotes the evolution of cooperation. We engineer an experimental Prisoner's Dilemma game in the budding yeast Saccharomyces cerevisiae to show that, despite losing to defectors in nonexpanding conditions, cooperators increase in frequency in spatially expanding populations. Fluorescently labeled colonies show genetic demixing of cooperators and defectors, followed by increase in cooperator frequency as cooperator sectors overtake neighboring defector sectors. Together with lattice-based spatial simulations, our results suggest that spatial population expansion drives the evolution of cooperation by (1) increasing positive genetic assortment at population frontiers and (2) selecting for phenotypes maximizing local deme productivity. Spatial expansion thus creates a selective force whereby cooperator-enriched demes overtake neighboring defector-enriched demes in a "survival of the fastest". We conclude that colony growth alone can promote cooperation and prevent defection in microbes. Our results extend to other species with spatially restricted dispersal undergoing range expansion, including pathogens, invasive species, and humans.

q-bio.PE↗

arXiv2014

Thorotrast and in vivo thorium dioxide: numerical simulation of 30 years of alpha radiation absorption by the tissues near a large compact source

Background: The epidemiology of the slightly radioactive contrast agent named Thorotrast presents a very long latency period between the injection and the development of the related pathologies. It is an example of the more general problem posed by a radioactive internal contaminant whose effects are not noteworthy in the short term but become dramatic in the long period. A point that is still to be explored is fluctuations (in space and time) in the localized absorption of radiation by the tissues. Methods: A Monte Carlo simulation code has been developed to study over a 30 year period the daily absorption of alpha radiation by micrometer sized portions of tissue placed at a distance of 0-100 micrometers from a model source, that approximates a compact thorium dioxide source in liver or spleen whose size is larger or equal to 20 micrometers. The biological depletion of the daughter nuclei of the thorium series is taken into account. The initial condition assumes chemically purified natural thorium. Results: Most of the absorbed dose is concentrated in a 25 micrometer thick layer of tissue, adjacent to the source boundary. Fluctuations where a target region with a volume of 1 cube micrometer is hit by 3-5 alpha particles in a day or in a shorter period of time are relevant in a 1-10 micrometer thick layer of tissue adjacent to the source boundary, where their frequency is larger than the Poisson law prediction.

physics.med-ph↗

arXiv2011

Self-organizing magnetic beads for biomedical applications

In the field of biomedicine magnetic beads are used for drug delivery and to treat hyperthermia. Here we propose to use self-organized bead structures to isolate circulating tumor cells using lab-on-chip technologies. Typically blood flows past microposts functionalized with antibodies for circulating tumor cells. Creating these microposts with interacting magnetic beads makes it possible to tune the geometry in size, position and shape. We developed a simulation tool that combines micromagnetics and discrete particle dynamics, in order to design micropost arrays made of interacting beads. The simulation takes into account the viscous drag of the blood flow, magnetostatic interactions between the magnetic beads and gradient forces from external aligned magnets. We developed a particle-particle particle-mesh method for effective computation of the magnetic force and torque acting on the particles.

physics.bio-ph↗

arXiv2014

Realistic Thermodynamic and Statistical-Mechanical Measures for Neural Synchronization

Synchronized brain rhythms, associated with diverse cognitive functions, have been observed in electrical recordings of brain activity. Neural synchronization may be well described by using the population-averaged global potential $V_G$ in computational neuroscience. The time-averaged fluctuation of $V_G$ plays the role of a "thermodynamic" order parameter $\cal {O}$ used for describing the synchrony-asynchrony transition in neural systems. Population spike synchronization may be well visualized in the raster plot of neural spikes. The degree of neural synchronization seen in the raster plot is well measured in terms of a "statistical-mechanical" spike-based measure $M_s$ introduced by considering the occupation and the pacing patterns of spikes. The global potential $V_G$ is also used to give a reference global cycle for the calculation of $M_s$. Hence, $V_G$ becomes an important collective quantity because it is associated with calculation of both $\cal {O}$ and $M_s$. However, it is practically difficult to directly get $V_G$ in real experiments. To overcome this difficulty, instead of $V_G$, we employ the instantaneous population spike rate (IPSR) which can be obtained in experiments, and develop realistic thermodynamic and statistical-mechanical measures, based on IPSR, to make practical characterization of the neural synchronization in both computational and experimental neuroscience. Particularly, more accurate characterization of weak sparse spike synchronization can be achieved in terms of realistic statistical-mechanical IPSR-based measure, in comparison with the conventional measure based on $V_G$.

q-bio.NC↗

arXiv2013

A biomechanical model of swallowing for understanding the influence of saliva and food bolus viscosity on flavour release

After swallowing a liquid or a semi-liquid food product, a thin film responsible for the dynamic profile of aroma release coats the pharyngeal mucosa. The objective of the present article was to understand and quantify physical mechanisms explaining pharyngeal mucosa coating. An elastohydrodynamic model of swallowing was developed for Newtonian liquids that focused on the most occluded region of the pharyngeal peristaltic wave. The model took lubrication by a saliva film and mucosa deformability into account. Food bolus flow rate and generated load were predicted as functions of three dimensionless variables: the dimensionless saliva flow rate, the viscosity ratio between saliva and the food bolus, and the elasticity number. Considering physiological conditions, the results were applied to predict aroma release kinetics. Two sets of conditions were distinguished. The first one was obtained when the saliva film is thin, in which case food bolus viscosity has a strong impact on mucosa coating and on flavour release. More importantly, we demonstrated the existence of a second set of conditions. It was obtained when the saliva film is thick and the food bolus coating the mucosa is very diluted by saliva during the swallowing process and the impact of its viscosity on flavour release is weak. This last phenomenon explains physically in vivo observations for Newtonian food products found in the literature. Moreover, in this case, the predicted thickness of the mix of food bolus with saliva coating the mucosa is approximately of 20 $μ$m; value in agreement with orders of magnitude found in the literature.

physics.med-ph↗

arXiv2013

Kinetic approaches to lactose operon induction and bimodality

The quasi-equilibrium approximation is acceptable when molecular interactions are fast enough compared to circuit dynamics, but is no longer allowed when cellular activities are governed by rare events. A typical example is the lactose operon (lac), one of the most famous paradigms of transcription regulation, for which several theories still coexist to describe its behaviors. The lac system is generally analyzed by using equilibrium constants, contradicting single-event hypotheses long suggested by Novick and Weiner (1957). Enzyme induction as an all-or-none phenomenon. Proc. Natl. Acad. Sci. USA 43, 553-566) and recently refined in the study of (Choi et al., 2008. A stochastic single-molecule event triggers phenotype switching of a bacterial cell. Science 322, 442-446). In the present report, a lac repressor (LacI)-mediated DNA immunoprecipitation experiment reveals that the natural LacI-lac DNA complex built in vivo is extremely tight and long-lived compared to the time scale of lac expression dynamics, which could functionally disconnect the abortive expression bursts and forbid using the standard modes of lac bistability. As alternatives, purely kinetic mechanisms are examined for their capacity to restrict induction through: (i) widely scattered derepression related to the arrival time variance of a predominantly backward asymmetric random walk and (ii) an induction threshold arising in a single window of derepression without recourse to nonlinear multimeric binding and Hill functions. Considering the complete disengagement of the lac repressor from the lac promoter as the probabilistic consequence of a transient stepwise mechanism, is sufficient to explain the sigmoidal lac responses as functions of time and of inducer concentration. This sigmoidal shape can be misleadingly interpreted as a phenomenon of equilibrium cooperativity classically used to explain bistability, but which has been reported to be weak in this system.

q-bio.MN↗

arXiv2013

Molecular dynamics studies on the NMR and X-ray structures of rabbit prion protein wild-type and mutants

Prion diseases are invariably fatal and highly infectious neurodegenerative diseases that affect a wide variety of mammalian species such as sheep, goats, mice, humans, chimpanzees, hamsters, cattle, elks, deer, minks, cats, chicken, pigs, turtles, etc. These neurodegenerative diseases are caused by the conversion from a soluble normal cellular protein into insoluble abnormally folded infectious prions and the conversion is believed to involve conformational change from a predominantly alpha-helical protein to one rich in beta-sheet structure. Such conformational changes may be amenable to study by molecular dynamics (MD) techniques. For rabbits, classical studies show they have a low susceptibility to be infected, but in 2012 it was reported that rabbit prion can be generated (though not directly) and the rabbit prion is infectious and transmissible (Proceedings of the National Academy of Sciences USA 109(13): 5080-5). This paper studies the NMR and X-ray molecular structures of rabbit prion protein wild-type and mutants by MD techniques, in order to understand the specific mechanism of rabbit prion protein and rabbit prions.

q-bio.BM↗

arXiv2014

Modeling the functional network of primary intercellular Ca$^{2+}$ wave propagation in astrocytes and its application to study drug effects

We introduce a simple procedure of multivariate signal analysis to uncover the functional connectivity among cells composing a living tissue and describe how to apply it for extracting insight on the effect of drugs in the tissue. The procedure is based on the covariance matrix of time resolved activity signals. By determining the time-lag that maximizes covariance, one derives the weight of the corresponding connection between cells. Introducing simple constraints, it is possible to conclude whether pairs of cells are functionally connected and in which direction. After testing the method against synthetic data we apply it to study intercellular propagation of Ca$^{2+}$ waves in astrocytes following an external stimulus, with the aim of uncovering the functional cellular connectivity network. Our method proves to be particularly suited for this type of networking signal propagation where signals are pulse-like and have short time-delays, and is shown to be superior to standard methods, namely a multivariate Granger algorithm. Finally, based the statistical analysis of the connection weight distribution, we propose simple measures for assessing the impact of drugs on the functional connectivity between cells.

physics.bio-ph↗

arXiv2012

Statistical modelling of higher-order correlations in pools of neural activity

Simultaneous recordings from multiple neural units allow us to investigate the activity of very large neural ensembles. To understand how large ensembles of neurons process sensory information, it is necessary to develop suitable statistical models to describe the response variability of the recorded spike trains. Using the information geometry framework, it is possible to estimate higher-order correlations by assigning one interaction parameter to each degree of correlation, leading to a $(2^N-1)$-dimensional model for a population with $N$ neurons. However, this model suffers greatly from a combinatorial explosion, and the number of parameters to be estimated from the available sample size constitutes the main intractability reason of this approach. To quantify the extent of higher than pairwise spike correlations in pools of multiunit activity, we use an information-geometric approach within the framework of the extended central limit theorem considering all possible contributions from high-order spike correlations. The identification of a deformation parameter allows us to provide a statistical characterisation of the amount of high-order correlations in the case of a very large neural ensemble, significantly reducing the number of parameters, avoiding the sampling problem, and inferring the underlying dynamical properties of the network within pools of multiunit neural activity.

q-bio.NC↗

arXiv2013

Unzipping of DNA under the influence of external fields

We study the features on the unzipping process of a modified version of the Peyrard-Bishop- Dauxois model. We show that the inclusion of a barrier in the on-site potential allows for the existence of stable domain wall solutions between open and closed regions of the DNA chain. We analyze the linear stability of such solutions and study their relevance in the dynamical behavior of DNA under ac forces.

physics.bio-ph↗

arXiv2013

Guided self-assembly of magnetic beads for biomedical applications

Micromagnetic beads are widely used in biomedical applications for cell separation, drug delivery, and hypothermia cancer treatment. Here we propose to use self-organized magnetic bead structures which accumulate on fixed magnetic seeding points to isolate circulating tumor cells. The analysis of circulating tumor cells is an emerging tool for cancer biology research and clinical cancer management including the detection, diagnosis and monitoring of cancer. Microfluidic chips for isolating circulating tumor cells use either affinity, size or density capturing methods. We combine multiphysics simulation techniques to understand the microscopic behavior of magnetic beads interacting with Nickel accumulation points used in lab-on-chip technologies. Our proposed chip technology offers the possibility to combine affinity and size capturing with special antibody-coated bead arrangements using a magnetic gradient field created by Neodymium Iron Boron permanent magnets. The multiscale simulation environment combines magnetic field computation, fluid dynamics and discrete particle dynamics.

physics.bio-ph↗

arXiv2013

New insights in gill/buccal rhythm spiking activity and CO2 sensitivity in pre- and post-metamorphic tadpoles (Pelophylax ridibundus)

Central CO2chemosensitivity is crucial for all air-breathing vertebrates and raises the question of itsrole in ventilatory rhythmogenesis. In this study, neurograms of ventilatory motor outputs recorded infacial nerve of premetamorphic and postmetamorphic tadpole isolated brainstems, under normo- andhypercapnia, are investigated using Continuous Wavelet Transform spectral analysis for buccal activityand computation of number and amplitude of spikes during buccal and lung activities. Buccal burstsexhibit fast oscillations (20-30 Hz) that are prominent in premetamorphic tadpoles: they result from thepresence in periodic time windows of high amplitude spikes. Hypercapnia systematically decreases thefrequency of buccal rhythm in both pre- and postmetamorphic tadpoles, by a lengthening of the interburstduration. In postmetamorphic tadpoles, hypercapnia reduces buccal burst amplitude and unmasks smallfast oscillations. Our results suggest a common effect of the hypercapnia on the buccal part of the CentralPattern Generator in all tadpoles and a possible effect at the level of the motoneuron recruitment inpostmetamorphic tadpoles.

q-bio.NC↗

arXiv2013

Adaptation and learning of molecular networks as a description of cancer development at the systems-level: Potential use in anti-cancer therapies

There is a widening recognition that cancer cells are products of complex developmental processes. Carcinogenesis and metastasis formation are increasingly described as systems-level, network phenomena. Here we propose that malignant transformation is a two-phase process, where an initial increase of system plasticity is followed by a decrease of plasticity at late stages of carcinogenesis as a model of cellular learning. We describe the hallmarks of increased system plasticity of early, tumor initiating cells, such as increased noise, entropy, conformational and phenotypic plasticity, physical deformability, cell heterogeneity and network rearrangements. Finally, we argue that the large structural changes of molecular networks during cancer development necessitate a rather different targeting strategy in early and late phase of carcinogenesis. Plastic networks of early phase cancer development need a central hit, while rigid networks of late stage primary tumors or established metastases should be attacked by the network influence strategy, such as by edgetic, multi-target, or allo-network drugs. Cancer stem cells need special diagnosis and targeting, since their dormant and rapidly proliferating forms may have more rigid, or more plastic networks, respectively. The extremely high ability to change their rigidity/plasticity may be a key differentiating hallmark of cancer stem cells. The application of early stage-optimized anti-cancer drugs to late-stage patients may be a reason of many failures in anti-cancer therapies. Our hypotheses presented here underlie the need for patient-specific multi-target therapies applying the correct ratio of central hits and network influences -- in an optimized sequence.

q-bio.MN↗

arXiv2014

Superparamagnetic iron oxide polyacrylic acid coated γ-Fe2O3 nanoparticles does not affect kidney function but causes acute effect on the cardiovascular function in healthy mice

This study describes the distribution of intravenously injected polyacrylic acid (PAA) coated γ-Fe2O3 NPs (10 mg kg-1) at the organ, cellular and subcellular levels in healthy BALB/cJ mice and in parallel addresses the effects of NP injection on kidney function, blood pressure and vascular contractility. Magnetic resonance imaging (MRI) and transmission electron microscopy (TEM) showed accumulation of NPs in the liver within 1h after intravenous infusion, accommodated by intracellular uptake in endothelial and Kupffer cells with subsequent intracellular uptake in renal cells, particularly the cytoplasm of the proximal tubule, in podocytes and mesangial cells. The renofunctional effects of NPs were evaluated by arterial acid-base status and measurements of glomerular filtration rate (GFR) after instrumentation with chronically indwelling catheters. Arterial pH was 7.46 and 7.41 in mice 0.5 h after injections of saline or NP, and did not change over the next 12h. In addition, the injections of NP did not affect arterial PCO2 or [HCO3-] either. Twenty-four and 96h after NP injections, the GFR averaged 11.0 and 13.0 ml min-1 g-1, respectively, values which were statistically comparable with controls (14.0 and 14.0 ml min-1 g-1). Mean arterial blood pressure (MAP) decreased 12-24h after NP injections (111 vs 123 min-1) associated with a decreased contractility of small mesenteric arteries revealed by myography to characterise endothelial function. In conclusion, our study demonstrates that accumulation of superparamagnetic iron oxide nanoparticles does not affect kidney function in healthy mice but temporarily decreases blood pressure.

physics.med-ph↗

arXiv2013

Low-Reynolds number swimming in a capillary tube

We use the boundary element method to study the low-Reynolds number locomotion of a spherical model microorganism in a circular tube. The swimmer propels itself by tangen- tial or normal surface motion in a tube whose radius is on the order of the swimmer size. Hydrodynamic interactions with the tube walls significantly affect the average swimming speed and power consumption of the model microorganism. In the case of swimming parallel to the tube axis, the locomotion speed is always reduced (resp. increased) for swimmers with tangential (resp. normal) deformation. In all cases, the rate of work nec- essary for swimming is increased by confinement. Swimmers with no force-dipoles in the far field generally follow helical trajectories, solely induced by hydrodynamic interactions with the tube walls, and in qualitative agreement with recent experimental observations for Paramecium. Swimmers of the puller type always display stable locomotion at a lo- cation which depends on the strength of their force dipoles: swimmers with weak dipoles (small α) swim in the centre of the tube while those with strong dipoles (large α) swim near the walls. In contrast, pusher swimmers and those employing normal deformation are unstable and end up crashing into the walls of the tube. Similar dynamics is observed for swimming into a curved tube. These results could be relevant for the future design of artificial microswimmers in confined geometries.

physics.flu-dyn↗

arXiv2014

Stochastic dynamics of active swimmers in linear flows

Most classical work on the hydrodynamics of low-Reynolds-number swimming addresses deterministic locomotion in quiescent environments. Thermal fluctuations in fluids are known to lead to a Brownian loss of the swimming direction. As most cells or synthetic swimmers are immersed in external flows, we consider theoretically in this paper the stochastic dynamics of a model active particle (a self-propelled sphere) in a steady general linear flow. The stochasticity arises both from translational diffusion in physical space, and from a combination of rotary diffusion and run-and-tumble dynamics in orientation space. We begin by deriving a general formulation for all components of the long-time mean square displacement tensor for a swimmer with a time-dependent swimming velocity and whose orientation decorrelates due to rotary diffusion alone. This general framework is applied to obtain the convectively enhanced mean-squared displacements of a steadily-swimming particle in three canonical linear flows (extension, simple shear, and solid-body rotation). We then show how to extend our results to the case where the swimmer orientation also decorrelates on account of run-and-tumble dynamics. Self-propulsion in general leads to the same long-time temporal scalings as for passive particles in linear flows but with increased coefficients. In the particular case of solid-body rotation, the effective long-time diffusion is the same as that in a quiescent fluid, and we clarify the lack of flow-dependence by briefly examining the dynamics in elliptic linear flows. By comparing the new active terms with those obtained for passive particles we see that swimming can lead to an enhancement of the mean-square displacements by orders of magnitude, and could be relevant for biological organisms or synthetic swimming devices in fluctuating environmental or biological flows.

physics.flu-dyn↗

arXiv2014

Phoretic self-propulsion at finite Péclet numbers

Phoretic self-propulsion is a unique example of force- and torque-free motion on small scales. The classical framework describing the flow field around a particle swimming by self-diffusiophoresis neglects the advection of the solute field by the flow and assumes that the chemical interaction layer is thin compared to the particle size. In this paper we quantify and characterize the effect of solute advection on the phoretic swimming of a sphere. We first rigorously derive the regime of validity of the thin-interaction layer assumption at finite values of the Péclet number (Pe). Within this assumption, we solve computationally the flow around Janus phoretic particles and examine the impact of solute advection on propulsion and the flow created by the particle. We demonstrate that although advection always leads to a decrease of the swimming speed and flow stresslet at high values of the Péclet number, an increase can be obtained at intermediate values of Pe. This possible enhancement of swimming depends critically on the nature of the chemical interactions between the solute and the surface. We then derive an asymptotic analysis of the problem at small Pe allowing to rationalize our computational results. Our computational and theoretical analysis is accompanied by a parallel study of the role of reactive effects at the surface of the particle on swimming (Damköhler number).

physics.flu-dyn↗

arXiv2013

Mixing and transport by ciliary carpets: a numerical study

We use a 3D computational model to study the fluid transport and mixing due to the beating of an infinite array of cilia. In accord with recent experiments, we observe two distinct regions: a fluid transport region above the cilia and a fluid mixing region below the cilia tip. The metachronal wave due to phase differences between neighboring cilia is known to enhance the fluid transport above the ciliary tip. In this work, we show that the metachronal wave also enhances the mixing rates in the sub-ciliary region, often simultaneously with the flow rate enhancement. Our results suggest that this simultaneous enhancement in transport and mixing is due to an enhancement in shear flow. As the flow above the cilia increases, shear rate in the fluid increases and such shear enhances stretching, which is an essential ingredient for mixing. Estimates of the mixing time scale indicate that, compared to diffusion, the mixing due to the cilia beat may be significant and sometimes dominates chemical diffusion.

physics.flu-dyn↗