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Biomedical subjects

Pierre Sens

Publications and source records attributed to Pierre Sens.

8 recordsLinked to original sources

Two-chamber AFM: probing membrane proteins separating two aqueous compartments.

Biological membranes compartmentalize and define physical borders of cells. They are crowded with membrane proteins that fulfill diverse crucial functions. About one-third of all genes in organisms code for, and the majority of drugs target, membrane proteins. To combine structure and function analysis of membrane proteins, we designed a two-chamber atomic force microscopy (AFM) setup that allows investigation of membranes spanned over nanowells, therefore separating two aqueous chambers. We imaged nonsupported surface layers (S layers) of Corynebacterium glutamicum at sufficient resolution to delineate a 15 A-wide protein pore. We probed the elastic and yield moduli of nonsupported membranes, giving access to the lateral interaction energy between proteins. We combined AFM and fluorescence microscopy to demonstrate the functionality of proteins in the setup by documenting proton pumping by Halobacterium salinarium purple membranes.

Binding Sites↗

Chromosome oscillations in mitosis.

The motion and positioning of chromosomes during eukaryotic cell division is investigated theoretically. We perform a self-contained analysis where the motion of mono-oriented chromosomes results from the competition between the kinetochore and chromokinesin motors on the chromosome arms. We show that the interplay between the asterlike morphology of the mitotic spindle and the collective dynamics of motors accounts for chromosome motion, positioning, and congression. In particular, the characteristic oscillations of chromosomes observed in vivo arise naturally within this description.

Binding, Competitive↗

Budded membrane microdomains as tension regulators.

We propose a mechanism by which changes of the mechanical tension of a composite lipid membrane are buffered by the invagination of membrane domains. We show that domain invagination, driven by differences in chemical composition, is a first-order transition controlled by membrane tension. The invaginated domains play the role of a membrane reservoir, exchanging area with the main membrane, and impose an equilibrium tension entirely controlled by their mechanical properties. The dynamical response of the reservoir reflects the tension-dependent kinetics of the domain shape transition, so that the tension of such a composite membrane is inherently transient and dynamical. The implications of this phenomenon for the mechanical properties of the membranes of living cells, where invaginated membrane domains are known to exist, are discussed.

Computer Simulation↗

Nonequilibrium raftlike 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 domains can 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.

Journal Article↗

Gating-by-tilt of mechanically sensitive 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 k(B)T and is comparable to what is available under simple dilational gating. Recent experiments demonstrate that membrane leaflet asymmetries (spontaneous curvature) can strongly affect the gating of some channels. Such a phenomenon would be easier to explain under gating-by-tilt, given its novel intrinsic sensitivity to such asymmetry.

Cell Membrane↗

Dynamics of nonequilibrium 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 nonequilibrium structures (buds), for which a dynamical size selection is observed. A preferred size in the microm range is predicted, as a signature of the crossover between membrane and solvent dominated dynamical membrane response.

Cell Membrane↗

Theoretical model for the formation of caveolae and similar membrane invaginations.

We study a physical model for the formation of bud-like invaginations on fluid lipid membranes under tension, and apply this model to caveolae formation. We demonstrate that budding can be driven by membrane-bound proteins, provided that they exert asymmetric forces on the membrane that give rise to bending moments. In particular, caveolae formation does not necessarily require forces to be applied by the cytoskeleton. Our theoretical model is able to explain several features observed experimentally in caveolae, where proteins in the caveolin family are known to play a crucial role in the formation of caveolae buds. These include 1), the formation of caveolae buds with sizes in the 100-nm range and 2), that certain N- and C-termini deletion mutants result in vesicles that are an order-of-magnitude larger. Finally, we discuss the possible origin of the morphological striations that are observed on the surfaces of the caveolae.

Animals↗

Undulation instability of lipid membranes under an electric field.

The influence of an external 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 is derived and the electrohydrodynamic instability of a free floating membrane is studied. We find a most unstable mode of undulation, of wavelength in the microm range, connected to the crossover between membrane and solvent dominated dissipations.

Elasticity↗