arXiv subjects

Pierre Sens

Publications and source records attributed to Pierre Sens.

53 records · Page 3Linked to original sources

arXiv2013

Quantitative analysis of intra-Golgi transport reveals inter-cisternal exchange for all cargo

The mechanisms controlling the transport of proteins across the Golgi stack of mammalian and plant cells is the subject of intense debate, with two models, cisternal progression and inter-cisternal exchange, emerging as major contenders. A variety of transport experiments have claimed support for each of these models. We reevaluate these experiments using a single quantitative coarse-grained framework of intra-Golgi transport that accounts for both transport models and their many variants. Our analysis makes a definitive case for the existence of inter-cisternal exchange both for small membrane proteins (VSVG) and large protein complexes (procollagen) -- this implies that membrane structures larger than the typical protein-coated vesicles must be involved in transport. Notwithstanding, we find that current observations on protein transport cannot rule out cisternal progression as contributing significantly to the transport process. To discriminate between the different models of intra-Golgi transport, we suggest experiments and an analysis based on our extended theoretical framework that compare the dynamics of transiting and resident proteins.

q-bio.SC↗

arXiv2012

Entropic Tension in Crowded Membranes

Unlike their model membrane counterparts, biological membranes are richly decorated with a heterogeneous assembly of membrane proteins. These proteins are so tightly packed that their excluded area interactions can alter the free energy landscape controlling the conformational transitions suffered by such proteins. For membrane channels, this effect can alter the critical membrane tension at which they undergo a transition from a closed to an open state, and therefore influence protein function \emph{in vivo}. Despite their obvious importance, crowding phenomena in membranes are much less well studied than in the cytoplasm. Using statistical mechanics results for hard disk liquids, we show that crowding induces an entropic tension in the membrane, which influences transitions that alter the projected area and circumference of a membrane protein. As a specific case study in this effect, we consider the impact of crowding on the gating properties of bacterial mechanosensitive membrane channels, which are thought to confer osmoprotection when these cells are subjected to osmotic shock. We find that crowding can alter the gating energies by more than $2\;k_BT$ in physiological conditions, a substantial fraction of the total gating energies in some cases. Given the ubiquity of membrane crowding, the nonspecific nature of excluded volume interactions, and the fact that the function of many membrane proteins involve significant conformational changes, this specific case study highlights a general aspect in the function of membrane proteins.

physics.bio-ph↗

arXiv2011

Reversibility of Red blood Cell deformation

The ability of cells to undergo reversible shape changes is often crucial to their survival. For Red Blood Cells (RBCs), irreversible alteration of the cell shape and flexibility often causes anemia. Here we show theoretically that RBCs may react irreversibly to mechanical perturbations because of tensile stress in their cytoskeleton. The transient polymerization of protein fibers inside the cell seen in sickle cell anemia or a transient external force can trigger the formation of a cytoskeleton-free membrane protrusion of micrometer dimensions. The complex relaxation kinetics of the cell shape is shown to be responsible for selecting the final state once the perturbation is removed, thereby controlling the reversibility of the deformation. In some case, tubular protrusion are expected to relax via a peculiar "pearling instability".

q-bio.CB↗

arXiv2011

Cooperative protein transport in cellular organelles

Compartmentalization into biochemically distinct organelles constantly exchanging material is one of the hallmarks of eukaryotic cells. In the most naive picture of inter-organelle transport driven by concentration gradients, concentration differences between organelles should relax. We determine the conditions under which cooperative transport, i.e. based on molecular recognition, allows for the existence and maintenance of distinct organelle identities. Cooperative transport is also shown to control the flux of material transiting through a compartmentalized system, dramatically increasing the transit time under high incoming flux. By including chemical processing of the transported species, we show that this property provides a strong functional advantage to a system responsible for protein maturation and sorting.

q-bio.SC↗

arXiv2010

Microphase separation in nonequilibrium biomembranes

Microphase separation of membrane components is thought to play an important role in many physiological processes, from cell signaling to endocytosis and cellular trafficking. Here, we study how variations in the membrane composition can be driven by fluctuating forces. We show that the membrane steady state is not only controlled by the strength of the forces and how they couple to the membrane, but also by their dynamics: In a simple class of models this is captured by a single a correlation time. We conclude that the coupling of membrane composition to normal mechanical forces, such as might be exerted by polymerizing cytoskeleton filaments, could play an important role in controlling the steady state of a cell membrane that exhibits transient microphase separation on lengthscales in the 10-100 nm regime.

q-bio.SC↗

arXiv2008

Kinetic regulation of coated vesicle secretion

The secretion of vesicles for intracellular transport often rely on the aggregation of specialized membrane-bound proteins into a coat able to curve cell membranes. The nucleation and growth of a protein coat is a kinetic process that competes with the energy-consuming turnover of coat components between the membrane and the cytosol. We propose a generic kinetic description of coat assembly and the formation of coated vesicles, and discuss its implication to the dynamics of COP vesicles that traffic within the Golgi and with the Endoplasmic Reticulum. We show that stationary coats of fixed area emerge from the competition between coat growth and the recycling of coat components, in a fashion resembling the treadmilling of cytoskeletal filaments. We further show that the turnover of coat components allows for a highly sensitive switching mechanism between a quiescent and a vesicle producing membrane, upon a slowing down of the exchange kinetics. We claim that the existence of this switching behaviour, also triggered by factors such as the presence of cargo and variation of the membrane mechanical tension, allows for efficient regulation of vesicle secretion. We propose a model, supported by different experimental observations, in which vesiculation of secretory membranes is impaired by the energy consuming desorption of coat proteins, until the presence of cargo or other factors triggers a dynamical switch into a vesicle producing state.

q-bio.SC↗

arXiv2007

Asynchronous Implementation of Failure Detectors with partial connectivity and unknown participants

We consider the problem of failure detection in dynamic networks such as MANETs. Unreliable failure detectors are classical mechanisms which provide information about process failures. However, most of current implementations consider that the network is fully connected and that the initial number of nodes of the system is known. This assumption is not applicable to dynamic environments. Furthermore, such implementations are usually timer-based while in dynamic networks there is no upper bound for communication delays since nodes can move. This paper presents an asynchronous implementation of a failure detector for unknown and mobile networks. Our approach does not rely on timers and neither the composition nor the number of nodes in the system are known. We prove that our algorithm can implement failure detectors of class <>S when behavioral properties and connectivity conditions are satisfied by the underlying system.

cs.DC↗

arXiv2006

Force balance and membrane shedding at the Red Blood Cell surface

During the aging of the red-blood cell, or under conditions of extreme echinocytosis, membrane is shed from the cell plasma membrane in the form of nano-vesicles. We propose that this process is the result of the self-adaptation of the membrane surface area to the elastic stress imposed by the spectrin cytoskeleton, via the local buckling of membrane under increasing cytoskeleton stiffness. This model introduces the concept of force balance as a regulatory process at the cell membrane, and quantitatively reproduces the rate of area loss in aging red-blood cells.

q-bio.CB↗

arXiv2005

Budded membrane microdomains as regulators for cellular tension

We propose a mechanism for mechanical regulation at the membrane of living cells, based on the exchange of membrane area between the cell membrane and a membrane reservoir. The reservoir is composed of invaginated membrane microdomains which are liable to flatten upon increase of membrane strain, effectively controlling membrane tension. We show that the domain shape transition is first order, allowing for coexistence between flat and invaginated domains. During coexistence, the membrane tension is controlled by the domains elasticity and by the kinetics of the shape transition. We show that the tension of the plasma membrane of living cells is inherently transient and dynamical, and that valuable insights into the organization of the cell membrane can be obtained by studying the variation of the cell membrane tension upon mechanical perturbation.

q-bio.SC↗

arXiv2005

Chromosome Oscillations in Mitosis

Successful cell division requires a tight regulation of chromosome motion via the activity of molecular motors. Many of the key players at the origin of the forces generating the movement have been identified, but their spatial and temporal organization remains elusive. The protein complex Kinetochore on the chromosome associates with microtubules emanating from one of the spindle poles and drives the chromosome toward the pole. Chromokinesin motors on the chromosome arms also interact with microtubules, ejecting the chromosome away from the pole. In animal cells, a monooriented chromosome (associated to a single pole) periodically switches between phases of poleward and away from the pole movement[, a behavior tentatively explained so far by the existence of a complex switching mechanism within the kinetochore itself. Here we show that the interplay between the morphology of the mitotic spindle and the collective kinetics of chromokinesins can account for the highly non-linear periodic chromosome motion. Our analysis provides a natural explanation for the origin of chromosome directional instability and for the mechanism by which chromosomes feel their position in space.

q-bio.SC↗

arXiv2005

Non-equilibrium raft-like membrane domains under continuous recycling

We present a model for the kinetics of spontaneous membrane domain (raft) assembly that includes the effect of membrane recycling ubiquitous in living cells. We show that the domains have a broad power-law distribution with an average radius that scales with the 1/4 power of the domain lifetime when the line tension at the domain edges is large. For biologically reasonable recycling and diffusion rates the average domain radius is in the tens of nm range, consistent with observations. This represents one possible link between signaling (involving rafts) and traffic (recycling) in cells. Finally, we present evidence that suggests that the average raft size may be the same for all scale-free recycling schemes.

cond-mat.soft↗

arXiv2003

Dynamics of non-equilibrium membrane bud formation

The dynamical response of a lipid membrane to a local perturbation of its molecular symmetry is investigated theoretically. A density asymmetry between the two membrane leaflets is predominantly released by in-plane lipid diffusion or membrane curvature, depending upon the spatial extent of the perturbation. It may result in the formation of non-equilibrium structures (buds), for which a dynamical size selection is observed. A preferred size in the micrometer range is predicted, as a signature of the crossover between membrane and solvent dominated dynamical membrane response.

cond-mat.soft↗

arXiv2003

Gating-by-tilt of mechanosensitive membrane channels

We propose an alternative mechanism for the gating of biological membrane channels in response to membrane tension that involves a change in the slope of the membrane near the channel. Under biological membrane tensions we show that the energy difference between the closed (tilted) and open (untilted) states can far exceed kBT and is comparable to what is available under simple ilational gating. Recent experiments demonstrate that membrane leaflet asymmetries (spontaneous curvature) can strong effect the gating of some channels. Such a phenomenon would be more easy to explain under gating-by-tilt, given its novel intrinsic sensitivity to such asymmetry.

cond-mat.soft↗

arXiv2001

Undulation instability of lipid membranes under an electric field

The influence of an electric field on a poorly conductive membrane such as a lipid bilayer is studied theoretically. The unbalanced electric stress created by an ionic current across a non-perfectly flat membrane gives rise to a destabilizing surface energy enhancing undulations. The deformation of a membrane attached to a frame and the subsequent force on the frame are derived and the electrohydrodynamic instability of a free floating membrane is also studied. We find a most unstable mode of undulation, of wavelength in the $μm$ range, connected to the crossover between membrane and solvent dominated dissipations.

cond-mat.soft↗

arXiv2000

Structure Factor of a Lamellar Smectic Phase with Inclusions

Motivated by numerous X-ray scattering studies of lamellar phases with membrane proteins, amphiphilic peptides, polymers, or other inclusions, we have determined the modifications of the classical Caille law for a smectic phase as a function of the nature and concentration of inclusions added to it. Besides a fundamental interest on the behavior of fluctuating systems with inclusions, a precise characterization of the action of a given protein on a lipid membrane (anchoring, swelling, stiffening ...) is of direct biological interest and could be probed by way of X-ray measurements. As a first step we consider three different couplings involving local pinching (or swelling), stiffening or tilt of the membrane. In the first two cases we predict that independent inclusions induce a simple renormalization of the bending and compression modulii of the smectic phase. The X-ray experiments may also be used to probe correlations between inclusions. Finally we show that asymmetric coupling (such as a local tilt of the membrane) results in a modification of the usual Caille law.

cond-mat.soft↗

arXiv2000

Counter-ion release and electrostatic adsorption

The effective charge of a rigid polyelectrolyte (PE) approaching an oppositely charged surface is studied. The cases of a weak (annealed) and strongly charged PE with condensed counterions (such as DNA) are discussed. In the most interesting case of the adsorption onto a substrate of low dielectric constant (such as a lipid membrane or a mica sheet) the condensed counterions are not always released as the PE approaches the substrate, because of the major importance of the image charge effect. For the adsorption onto a surface with freely moving charges, the image charge effect becomes less important and full release is often expected.

cond-mat.soft↗

arXiv1999

Charge Distribution on Annealed Polyelectrolytes

We investigate the equilibrium charge distribution along a single annealed polyelectrolyte chain under different conditions. The coupling between the conformation of the chain and the local charge distribution is described for various solvent qualities and salt concentration. In salt free solution, we find a slight charge depletion in the central part of the chain: the charges accumulate at the ends. The effect is less important if salt is added to the solution since the charge inhomogeneity is localized close to the chain ends over a distance of order of the Debye length. In the case of poor solvent conditions we find a different charging of beads and strings in the framework of the necklace model. This inhomogeneity leads to a charge instability and a first order transition between spherical globules and elongated chains.

cond-mat.soft↗