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Pierre Sens

Publications and source records attributed to Pierre Sens.

At least 37 records · Page 2Linked to original sources

Dynamics of passive and active membrane tubes

Utilising Onsager's variational formulation, we derive dynamical equations for the relaxation of a fluid membrane tube in the limit of small deformation, allowing for a contrast of solvent viscosity across the membrane and variations in surface tension due to membrane incompressibility. We compute the relaxation rates, recovering known results in the case of purely axis-symmetric perturbations and making new predictions for higher order (azimuthal) $m$-modes. We analyse the long and short wavelength limits of these modes by making use of various asymptotic arguments. We incorporate stochastic terms to our dynamical equations suitable to describe both passive thermal forces and non-equilibrium active forces. We derive expressions for the fluctuation amplitudes, an effective temperature associated with active fluctuations, and the power spectral density for both the thermal and active fluctuations. We discuss an experimental assay that might enable measurement of these fluctuations to infer the properties of the active noise. Finally we discuss our results in the context of active membranes more generally and give an overview of some open questions in the field.

cond-mat.soft↗

Shear-driven instabilities of membrane tubes and dynamin-induced scission

Motivated by the mechanics of dynamin-mediated membrane tube fission we analyse the stability of fluid membrane tubes subjected to shear flow in azimuthal direction. We find a novel helical instability driven by the membrane shear flow which results in a non-equilibrium steady state for the tube fluctuations. This instability has its onset at shear rates that may be physiologically accessible under the action of dynamin and could also be probed using in-vitro experiments on membrane nanotubes, e.g. using magnetic tweezers. We discuss how such an instability may play a role in the mechanism for dynamin-mediated membrane tube fission.

physics.bio-ph↗

Stick-Slip model for actin-driven cell protrusions, cell polarisation and crawling

Cell crawling requires the generation of intracellular forces by the cytoskeleton and their transmission to an extracellular substrate through specific adhesion molecules. Crawling cells show many features of excitable systems, such as spontaneous symmetry breaking and crawling in the absence of external cues, and periodic and propagating waves of activity. Mechanical instabilities in the active cytoskeleton network and feedback loops in the biochemical network of activators and repressors of cytoskeleton dynamics have been invoked to explain these dynamical features. Here, we show that the interplay between the dynamics of cell-substrate adhesion and linear cellular mechanics is sufficient to reproduce many non-linear dynamical patterns observed in spreading and crawling cells. Using an analytical formalism of the molecular clutch model of cell adhesion, regulated by local mechanical forces, we show that cellular traction forces exhibit a stick-slip dynamics resulting in periodic waves of protrusion/retraction and propagating waves along the cell edge. This can explain spontaneous symmetry breaking and polarisation of spreading cells, leading to steady crawling or bipedal motion, and bistability, where persistent cell motion requires a sufficiently strong transient external stimulus. The model also highlight the role of membrane tension in providing the long-range mechanical communication across the cell required for symmetry breaking.

physics.bio-ph↗

Glycan processing in the Golgi -- optimal information coding and constraints on cisternal number and enzyme specificity

Many proteins that undergo sequential enzymatic modification in the Golgi cisternae are displayed at the plasma membrane as cell identity markers. The modified proteins, called glycans, represent a molecular code. The fidelity of this glycan code is measured by how accurately the glycan synthesis machinery realises the desired target glycan distribution for a particular cell type and niche. In this paper, we quantitatively analyse the tradeoffs between the number of cisternae and the number and specificity of enzymes, in order to synthesize a prescribed target glycan distribution of a certain complexity. We find that to synthesize complex distributions, such as those observed in real cells, one needs to have multiple cisternae and precise enzyme partitioning in the Golgi. Additionally, for fixed number of enzymes and cisternae, there is an optimal level of specificity of enzymes that achieves the target distribution with high fidelity. Our results show how the complexity of the target glycan distribution places functional constraints on the Golgi cisternal number and enzyme specificity.

q-bio.SC↗

Model of lamellipodium initiation during cell spreading

Cell spreading requires a major reorganisation of the actin cytoskeleton, from a cortical structure to a lamellipodium where filaments are mostly parallel to the substrate. We propose a model inspired by the physics of nematic liquid crystals and fluid membranes, in which the coupling between actin mechanics, filaments orientation, and the local curvature of the cell membrane naturally yields the collective reorientation of actin filaments at the highly curved edge of a spreading cell. Filament orientation increases the traction force exerted by the frictional flow of polymerising actin on the substrate, creating a positive feedback loop between edge curvature, filament alignment, and traction force that promotes cell spreading. We establish the condition under which this feedback leads to a full wetting transition, which we interpret as the initiation of a lamellipodium, and we uncover the existence of bi-stability between partial and full spreading which could trigger spontaneous cell polarization and lead to migration.

physics.bio-ph↗

Receptor-Mediated Endocytosis of a Cylindrical Nanoparticle in the Presence of Cytoskeleton Substrate

Internalization of particles by cells plays a crucial role for adsorbing nutrients and fighting infection. Endocytosis is one of the most important mechanisms of the particles uptake which encompass multiple pathways. Although endocytosis is a complex mechanism involving biochemical signaling and active force generation, the energetic cost associated to the large deformations of the cell membrane wrapping around the foreign particle is an important factor controlling this process, which can be studied using quantitative physical models. Of particular interest is the competition between membrane - cytoskeleton and membrane - target adhesion. Here, we explore the wrapping of a lipid membrane around a long cylindrical object in the presence of a substrate mimicking the cytoskeleton. Using discretization of the Helfrich elastic energy that accounts for the membrane bending rigidity and surface tension, we obtain a wrapping phase diagram as a function of the membrane-cytoskeleton and the membrane-target adhesion energy that includes unwrapped, partially wrapped and fully wrapped states. We provide an analytical expression for the boundary between the different regimes. While the transition to partial wrapping is independent of membrane tension, the transition to full wrapping is very much influenced by membrane tension. We also show that target wrapping may proceed in an asymmetric fashion in the full wrapping regime.

cond-mat.soft↗

A Bag-of-Tasks Scheduler Tolerant to Temporal Failures in Clouds

Cloud platforms have emerged as a prominent environment to execute high performance computing (HPC) applications providing on-demand resources as well as scalability. They usually offer different classes of Virtual Machines (VMs) which ensure different guarantees in terms of availability and volatility, provisioning the same resource through multiple pricing models. For instance, in Amazon EC2 cloud, the user pays per hour for on-demand VMs while spot VMs are unused instances available for lower price. Despite the monetary advantages, a spot VM can be terminated, stopped, or hibernated by EC2 at any moment. Using both hibernation-prone spot VMs (for cost sake) and on-demand VMs, we propose in this paper a static scheduling for HPC applications which are composed by independent tasks (bag-of-task) with deadline constraints. However, if a spot VM hibernates and it does not resume within a time which guarantees the application's deadline, a temporal failure takes place. Our scheduling, thus, aims at minimizing monetary costs of bag-of-tasks applications in EC2 cloud, respecting its deadline and avoiding temporal failures. To this end, our algorithm statically creates two scheduling maps: (i) the first one contains, for each task, its starting time and on which VM (i.e., an available spot or on-demand VM with the current lowest price) the task should execute; (ii) the second one contains, for each task allocated on a VM spot in the first map, its starting time and on which on-demand VM it should be executed to meet the application deadline in order to avoid temporal failures. The latter will be used whenever the hibernation period of a spot VM exceeds a time limit. Performance results from simulation with task execution traces, configuration of Amazon EC2 VM classes, and VMs market history confirms the effectiveness of our scheduling and that it tolerates temporal failures.

cs.DC↗

VCube-PS: A Causal Broadcast Topic-based Publish/Subscribe System

In this work we present VCube-PS, a topic-based Publish/Subscribe system built on the top of a virtual hypercube-like topology. Membership information and published messages are broadcast to subscribers (members) of a topic group over dynamically built spanning trees rooted at the publisher. For a given topic, the delivery of published messages respects the causal order. VCube-PS was implemented on the PeerSim simulator, and experiments are reported including a comparison with the traditional Publish/Subscribe approach that employs a single rooted static spanning-tree for message distribution. Results confirm the efficiency of VCube-PS in terms of scalability, latency, number and size of messages.

cs.DC↗

Hydro-osmotic instabilities in active membrane tubes

We study a membrane tube with unidirectional ion pumps driving an osmotic pressure difference. A pressure driven peristaltic instability is identified, qualitatively distinct from similar tension-driven Rayleigh type instabilities on membrane tubes. We discuss how this instability could be related to the function and biogenesis of membrane bound organelles, in particular the contractile vacuole complex. The unusually long natural wavelength of this instability is in agreement with that observed in cells.

physics.bio-ph↗

Stochastic Models of Vesicular Sorting in Cellular Organelles

The proper sorting of membrane components by regulated exchange between cellular organelles is crucial to intra-cellular organisation. This process relies on the budding and fusion of transport vesicles, and should be strongly influenced by stochastic fluctuations considering the relatively small size of many organelles. We identify the perfect sorting of two membrane components initially mixed in a single compartment as a first passage process, and we show that the mean sorting time exhibits two distinct regimes as a function of the ratio of vesicle fusion to budding rates. Low ratio values lead to fast sorting, but results in a broad size distribution of sorted compartments dominated by small entities. High ratio values result in two well defined sorted compartments but is exponentially slow. Our results suggest an optimal balance between vesicle budding and fusion for the rapid and efficient sorting of membrane components, and highlight the importance of stochastic effects for the steady-state organisation of intra-cellular compartments.

physics.bio-ph↗

Stochastic Model of Maturation and Vesicular Exchange in Cellular Organelles

The dynamical organization of membrane-bound organelles along intracellular transport pathways relies on vesicular exchange between organelles and on biochemical maturation of the organelle content by specific enzymes. The relative importance of each mechanism in controlling organelle dynamics remains controversial, in particular for transport through the Golgi apparatus. Using a stochastic model, we show that full maturation of membrane-bound compartments can be seen as the stochastic escape from a steady-state in which export is dominated by vesicular exchange. We show that full maturation can contribute a significant fraction of the total out-flux for small organelles such as endosomes and Golgi cisternae.

physics.bio-ph↗

Analysis of a Stochastic Model of Replication in Large Distributed Storage Systems: A Mean-Field Approach

Distributed storage systems such as Hadoop File System or Google File System (GFS) ensure data availability and durability using replication. This paper is focused on the analysis of the efficiency of replication mechanism that determines the location of the copies of a given file at some server. The variability of the loads of the nodes of the network is investigated for several policies. Three replication mechanisms are tested against simulations in the context of a real implementation of a such a system: Random, Least Loaded and Power of Choice. The simulations show that some of these policies may lead to quite unbalanced situations: if $β$ is the average number of copies per node it turns out that, at equilibrium, the load of the nodes may exhibit a high variability. It is shown in this paper that a simple variant of a power of choice type algorithm has a striking effect on the loads of the nodes: at equilibrium, the distribution of the load of a node has a bounded support, most of nodes have a load less than $2β$ which is an interesting property for the design of the storage space of these systems. Mathematical models are introduced and investigated to explain this interesting phenomenon. The analysis of these systems turns out to be quite complicated mainly because of the large dimensionality of the state spaces involved. Our study relies on probabilistic methods, mean-field analysis, to analyze the asymptotic behavior of an arbitrary node of the network when the total number of nodes gets large. An additional ingredient is the use of stochastic calculus with marked Poisson point processes to establish some of our results.

cs.DC↗

Model for probing membrane-cortex adhesion by micropipette aspiration and fluctuation spectroscopy

We propose a model for membrane-cortex adhesion which couples membrane deformations, hydrodynamics and kinetics of membrane-cortex ligands. In its simplest form, the model gives explicit predictions for the critical pressure for membrane detachment and for the value of adhesion energy. We show that these quantities exhibit a significant dependence on the active acto-myosin stresses. The model provides a simple framework to access quantitative information on cortical activity by means of micropipette experiments. We also extend the model to incorporate fluctuations and show that detailed information on the stability of membrane-cortex coupling can be obtained by a combination of micropipette aspiration and fluctuation spectroscopy measurements.

physics.bio-ph↗

The Weakest Failure Detector for Eventual Consistency

In its classical form, a consistent replicated service requires all replicas to witness the same evolution of the service state. Assuming a message-passing environment with a majority of correct processes, the necessary and sufficient information about failures for implementing a general state machine replication scheme ensuring consistency is captured by the Ω failure detector. This paper shows that in such a message-passing environment, Ω is also the weakest failure detector to implement an eventually consistent replicated service, where replicas are expected to agree on the evolution of the service state only after some (a priori unknown) time. In fact, we show that Ω is the weakest to implement eventual consistency in any message-passing environment, i.e., under any assumption on when and where failures might occur. Ensuring (strong) consistency in any environment requires, in addition to Ω, the quorum failure detector Σ. Our paper thus captures, for the first time, an exact computational difference be- tween building a replicated state machine that ensures consistency and one that only ensures eventual consistency.

cs.DC↗

The Impact Failure Detector

This work proposes a new and flexible unreliable failure detector whose output is related to the trust level of a set of processes. By expressing the relevance of each process of the set by an impact factor value, our approach allows the tuning of the detector output, making possible a softer or stricter monitoring. The idea behind our proposal is that, according to an acceptable margin of failures and the impact factor assigned to processes, in some scenarios, the failure of some low impact processes may not change the user confidence in the set of processes, while the crash of a high impact factor process may seriously affect it. We outline the application scenarios and the proposed unreliable failure detector, giving a detailed account of the concept on which it is based.

cs.DC↗

Finite size effects in non-equilibrium membrane phase separation

The formation of dynamical clusters of proteins is ubiquitous in cellular membranes and is in part regulated by the recycling of membrane components. Mean-field models of out-of-equilibrium cluster formation with recycling predict a broad cluster size distribution for infinite systems and must be corrected for finite-size effects for small systems such as cellular organelles. We show, using stochastic simulations and analytic modelling, that tuning the system size is an efficient way to control the size of lateral membrane heterogeneities. We apply these findings to a chain of enzymatic reaction sensitive to membrane protein clustering. The reaction efficiency is found to be a non-monotonic function of the system size, and can be optimal for sizes comparable to those of cellular organelles.

cond-mat.soft↗

Rigidity sensing by stochastic sliding friction

The sliding friction force exerted by stochastic linkers interacting with a moving filament is calculated. The elastic properties of the substrate on which the linkers are anchored are shown to strongly influence the friction force. In some cases, the force is maximal for a finite substrate rigidity. Collective effects give rise to a dynamical instability resulting in a stick-slip behaviour, which is substrate-sensitive. The relevance of these results for the motility of crawling cells powered by an actin retrograde flow is discussed.

cond-mat.soft↗

Transient domain formation in membrane-bound organelles undergoing maturation

The membrane components of cellular organelles have been shown to segregate into domains as the result of biochemical maturation. We propose that the dynamical competition between maturation and lateral segregation of membrane components regulates domain formation. We study a two- component fluid membrane in which enzymatic reaction irreversibly converts one component into another, and phase separation triggers the formation of transient membrane domains. The maximum domains size is shown to depend on the maturation rate as a power-law similar to the one observed for domain growth with time in the absence of maturation, despite this time dependence not being verified in the case of irreversible maturation. This control of domain size by enzymatic activity could play a critical role in intra-organelle dynamics.

q-bio.SC↗