Model of Cell Crawling Controlled by Mechanosensitive Adhesion.

We study the motility of model cells and biomimetic soft objects crawling over a substrate covered with adhesive linkers. The cell exerts traction forces on the substrate through the active periodic motion of molecular complexes to which the linkers bind and unbind stochastically. We first show that the diffusion coefficient of a force dipole (unable by symmetry to perform directed motion) is maximal for a finite ratio of the unbinding to binding rates, highlighting the role of adhesion kinetics on cell translocation. We next show that cells exerting more complex traction force distributions may exhibit directed motion only if the linkers are mechanosensitive, i.e., if the bonds' lifetime decreases (slip bonds) or increases (catch bonds) under stress. The average migration speed is higher in the catch-bond regime but so are the fluctuations, yielding a biased diffusive motion characterized by a Peclet number smaller than in the slip-bond regime.

Fluctuations of a membrane nanotube revealed by high-resolution force measurements.

Pulling membrane nanotubes from liposomes presents a powerful method to gain access to membrane mechanics. Here we extend classical optical tweezers studies to infer membrane nanotube dynamics with high spatial and temporal resolution. We first validate our force measurement setup by accurately measuring the bending modulus of EPC membrane in tube pulling experiments. Then we record the position signal of a trapped bead when it is connected, or not, to a tube. We derive the fluctuation spectrum of these signals and find that the presence of a membrane nanotube induces higher fluctuations, especially at low frequencies (10-1000 Hz). We analyse these spectra by taking into account the peristaltic modes of nanotube fluctuations. This analysis provides a new experimental framework for a quantitative study of the fluctuations of nanotubular membrane structures that are present in living cells, and now classically used for in vitro biomimetic approaches.

Polarization of cells and soft objects driven by mechanical interactions: consequences for migration and chemotaxis.

We study a generic model for the polarization and motility of self-propelled soft objects, biological cells, or biomimetic systems, interacting with a viscous substrate. The active forces generated by the cell on the substrate are modeled by means of oscillating force multipoles at the cell-substrate interface. Symmetry breaking and cell polarization for a range of cell sizes naturally "emerge" from long range mechanical interactions between oscillating units, mediated both by the intracellular medium and the substrate. However, the harnessing of cell polarization for motility requires substrate-mediated interactions. Motility can be optimized by adapting the oscillation frequency to the relaxation time of the system or when the substrate and cell viscosities match. Cellular noise can destroy mechanical coordination between force-generating elements within the cell, resulting in sudden changes of polarization. The persistence of the cell's motion is found to depend on the cell size and the substrate viscosity. Within such a model, chemotactic guidance of cell motion is obtained by directionally modulating the persistence of motion, rather than by modulating the instantaneous cell velocity, in a way that resembles the run and tumble chemotaxis of bacteria.

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 µm 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."

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 interorganelle 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.

Interactions between proteins bound to biomembranes.

We study a physical model for the interaction between general inclusions bound to fluid membranes that possess finite tension gamma, as well as the usual bending rigidity kappa. We are motivated by an interest in proteins bound to cell membranes that apply forces to these membranes, due to either entropic or direct chemical interactions. We find an exact analytic solution for the repulsive interaction between two similar circularly symmetric inclusions. This repulsion extends over length scales approximately sqrt[kappa/gamma] and contrasts with the membrane-mediated contact attraction for similar inclusions on tensionless membranes. For noncircularly symmetric inclusions we study the small, algebraically long-ranged, attractive contribution to the force that arises. We discuss the relevance of our results to biological phenomena, such as the budding of caveolae from cell membranes and the striations that are observed on their coats. These, and other, "gnarly buds" may prove fascinating to study further.

Hypereosinophilia-induced digital necrosis in a smoking patient.

Raynaud's phenomenon and digital necrosis of the fingers are rare complications of hypereosinophilia. We report a case of a smoking male who developed Raynaud's phenomenon and digital necrosis of the fingers associated with idiopathic hypereosinophilia with angiographically documented occlusion of small and medium arteries of the extremities. The eosinophils may play a thrombotic role in vascular pathology and eosinophil blood count should be checked when investigating patients with digital gangrene.

Counterion 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.

Myocardial bridging as a cause of acute transient left heart dysfunction.

The significance of myocardial bridging is still a matter of debate, and although several reports have underlined its pathologic potential, myocardial bridging is often considered to be a benign phenomenon. We present here the case of a 63-year-old woman with a history of acute left heart failure and ECG evidence of ischemia, and whose primary abnormality on extensive workup was myocardial bridging. This case further underlines that myocardial bridging can lead to significant cardiac events.

Inclusions on fluid membranes anchored to elastic media.

We model theoretically the effect of localized forces on a fluid membrane anchored to a uniform elastic medium. We use this as a simple model for the plasma membrane of a cell. The atomic force microscope (AFM) has been used to apply such forces, but large membrane perturbations occurring in vivo are also treated within the same framework. Inclusions of this nature may include cell junctions, filipodia, caveolae, and similar membrane invaginations. The breakdown of linear elastic response, as observed by AFM, is predicted to occur for forces as small as 10 pN. We estimate the position of this crossover and the subsequent nonlinear behavior and make encouraging quantitative comparison with experiments. Intrinsic membrane inclusions interact through their overlapping strain fields. For similar, point force-like inclusions at large separations, this yields an attractive potential that scales like the inverse of their separation. For membranes that are intrinsically stiff or under tension, the binding force between inclusions can depend on the properties of the membrane and may be large enough to induce aggregation of inclusions, as observed experimentally. For inclusions that fix the magnitude of the membrane deformation, rather than the applied force, we demonstrate the possibility of metastable states, corresponding to finite separations. Finally, we discuss briefly the case in which inclusions couple to the membrane in more complex ways, such as via a torque (twist). In such cases, the interaction scales like a higher power of the separation, depends on the orientation of the inclusions, and can have either sign.

[Attempt at diagnosis of hereditary spherocytosis using the ionophore valinomycin]. / Versuche zur Diagnostik der hereditären Sphärozytose mit Hilfe des Ionophors Valinomycin.

On the basis of former observations that erythrocytes of patients with hereditary spherocytosis (HS) exhibit a slighter K+ efflux under the influence of valinomycin and a diminished shrinking, the attempt was made to use this phenomenon in routine diagnostics. In pair comparison the findings already known could be proved impressively. However, obligatory limiting values which make it possible to dispense with giving statements of comparison could not be established. In this report the test is of limited value for haematological diagnostics.