Energetics of active fluctuations in living cells

The nonequilibrium activity taking place in a living cell can be monitored with a tracer embedded in the medium. While microrheology experiments based on optical manipulation of such probes have become increasingly standard, we put forward a number of experiments with alternative protocols that, we claim, will provide new insight into the energetics of active fluctuations. These are based on either performing thermodynamic--like cycles in control-parameter space, or on determining response to external perturbations of the confining trap beyond simple translation. We illustrate our proposals on an active itinerant Brownian oscillator modeling the dynamics of a probe embedded in a living medium

Fluctuations of internal energy flow in a vibrated granular gas

The non-equilibrium fluctuations of power flux in a fluidized granular media have been recently measured in an experiment [Phys. Rev. Lett. 92, 164301, 2004], which was announced to be a verification of the Fluctuation Relation (FR) by Gallavotti and Cohen. An effective temperature was also identified and proposed to be a useful probe for such non equilibrium systems. We explain these results in terms of a two temperature Poisson process. Within this model, supported by independent Molecular Dynamics simulations, power flux fluctuations do not satisfy the FR and the nature of the effective temperature is clarified. In the pursue of a hypothetical global quantity fulfilling the FR, this points to the need of considering other candidates than the power flux.Comment: accepted for publication on Physical Review Lette

Dynamics of a tracer granular particle as a non-equilibrium Markov process

The dynamics of a tracer particle in a stationary driven granular gas is investigated. We show how to transform the linear Boltzmann equation describing the dynamics of the tracer into a master equation for a continuous Markov process. The transition rates depend upon the stationary velocity distribution of the gas. When the gas has a Gaussian velocity probability distribution function (pdf), the stationary velocity pdf of the tracer is Gaussian with a lower temperature and satisfies detailed balance for any value of the restitution coefficient $\alpha$. As soon as the velocity pdf of the gas departs from the Gaussian form, detailed balance is violated. This non-equilibrium state can be characterized in terms of a Lebowitz-Spohn action functional $W(\tau)$ defined over trajectories of time duration $\tau$. We discuss the properties of this functional and of a similar functional $\bar{W}(\tau)$ which differs from the first for a term which is non-extensive in time. On the one hand we show that in numerical experiments, i.e. at finite times $\tau$, the two functionals have different fluctuations and $\bar{W}$ always satisfies an Evans-Searles-like symmetry. On the other hand we cannot observe the verification of the Lebowitz-Spohn-Gallavotti-Cohen (LS-GC) relation, which is expected for $W(\tau)$ at very large times $\tau$. We give an argument for the possible failure of the LS-GC relation in this situation. We also suggest practical recipes for measuring $W(\tau)$ and $\bar{W}(\tau)$ in experiments.Comment: 16 pages, 3 figures, submitted for publicatio

Exact solution of a model DNA-inversion genetic switch with orientational control

DNA inversion is an important mechanism by which bacteria and bacteriophage switch reversibly between phenotypic states. In such switches, the orientation of a short DNA element is flipped by a site-specific recombinase enzyme. We propose a simple model for a DNA inversion switch in which recombinase production is dependent on the switch state (orientational control). Our model is inspired by the fim switch in Escherichia coli. We present an exact analytical solution of the chemical master equation for the model switch, as well as stochastic simulations. Orientational control causes the switch to deviate from Poissonian behaviour: the distribution of times in the on state shows a peak and successive flip times are correlated.Comment: Revised version, accepted for publicatio

It is easy to see, but it is better to foresee: a case report on the favourable alliance between CardioMEMS and levosimendan

Abstract Background In the past years, different devices have been investigated to help in identifying early decompensation events in patients with heart failure (HF) and reduced ejection fraction (EF), reducing hospital admissions. In this report, we present the first patient experience with levosimendan infusion led by CardioMEMS. Case summary A 68-year-old man with HF and reduced EF with more than 20 hospitalizations for exacerbation of HF was enrolled in our HF Clinic from October 2017. Echocardiogram showed a dilated left ventricle with severely reduced EF (29%) and increased pulmonary artery systolic pressure (40 mmHg). From October 2017 to May 2019, the patient went through numerous hospitalizations, despite optimal medical therapy; subsequently, was adopted a strategy of levosimendan infusions guided by CardioMEMS. Levosimendan infusions improved haemodynamic and pressure profiles. The patient was monitored daily by CardioMEMS, and from June to December 2019, he had only two hospitalizations scheduled for levosimendan infusion and none for HF exacerbation. Discussion Our case supports the combination of CardioMEMS and levosimendan for the optimal management of patients with advanced HF. These results further strengthen the development of a randomized clinical trial to demonstrate the clinical usefulness of this device in combination with the levosimendan infusion programme in advanced HF patients

Switching and growth for microbial populations in catastrophic responsive environments

Phase variation, or stochastic switching between alternative states of gene expression, is common among microbes, and may be important in coping with changing environments. We use a theoretical model to assess whether such switching is a good strategy for growth in environments with occasional catastrophic events. We find that switching can be advantageous, but only when the environment is responsive to the microbial population. In our model, microbes switch randomly between two phenotypic states, with different growth rates. The environment undergoes sudden "catastrophes", the probability of which depends on the composition of the population. We derive a simple analytical result for the population growth rate. For a responsive environment, two alternative strategies emerge. In the "no switching" strategy, the population maximises its instantaneous growth rate, regardless of catastrophes. In the "switching" strategy, the microbial switching rate is tuned to minimise the environmental response. Which of these strategies is most favourable depends on the parameters of the model. Previous studies have shown that microbial switching can be favourable when the environment changes in an unresponsive fashion between several states. Here, we demonstrate an alternative role for phase variation in allowing microbes to maximise their growth in catastrophic responsive environments.Comment: 9 pages, 10 figures; replaced with revised versio

Active mechanics reveal molecular-scale force kinetics in living oocytes

Active diffusion of intracellular components is emerging as an important process in cell biology. This process is mediated by complex assemblies of molecular motors and cytoskeletal filaments that drive force generation in the cytoplasm and facilitate enhanced motion. The kinetics of molecular motors have been precisely characterized in-vitro by single molecule approaches, however, their in-vivo behavior remains elusive. Here, we study the active diffusion of vesicles in mouse oocytes, where this process plays a key role in nuclear positioning during development, and combine an experimental and theoretical framework to extract molecular-scale force kinetics (force, power-stroke, and velocity) of the in-vivo active process. Assuming a single dominant process, we find that the nonequilibrium activity induces rapid kicks of duration $\tau \sim$ 300 $\mu$s resulting in an average force of $F \sim$ 0.4 pN on vesicles in in-vivo oocytes, remarkably similar to the kinetics of in-vitro myosin-V. Our results reveal that measuring in-vivo active fluctuations allows extraction of the molecular-scale activity in agreement with single-molecule studies and demonstrates a mesoscopic framework to access force kinetics.Comment: 20 pages, 4 figures, see ancillary files for Supplementary Materials, * equally contributing author