Space dependent adhesion forces mediated by transient elastic linkages : new convergence and global existence results

In the first part of this work we show the convergence with respect to an asymptotic parameter {\epsilon} of a delayed heat equation. It represents a mathematical extension of works considered previously by the authors [Milisic et al. 2011, Milisic et al. 2016]. Namely, this is the first result involving delay operators approximating protein linkages coupled with a spatial elliptic second order operator. For the sake of simplicity we choose the Laplace operator, although more general results could be derived. The main arguments are (i) new energy estimates and (ii) a stability result extended from the previous work to this more involved context. They allow to prove convergence of the delay operator to a friction term together with the Laplace operator in the same asymptotic regime considered without the space dependence in [Milisic et al, 2011]. In a second part we extend fixed-point results for the fully non-linear model introduced in [Milisic et al, 2016] and prove global existence in time. This shows that the blow-up scenario observed previously does not occur. Since the latter result was interpreted as a rupture of adhesion forces, we discuss the possibility of bond breaking both from the analytic and numerical point of view

Numerical treatment of the Filament Based Lamellipodium Model (FBLM)

We describe in this work the numerical treatment of the Filament Based Lamellipodium Model (FBLM). The model itself is a two-phase two-dimensional continuum model, describing the dynamics of two interacting families of locally parallel F-actin filaments. It includes, among others, the bending stiffness of the filaments, adhesion to the substrate, and the cross-links connecting the two families. The numerical method proposed is a Finite Element Method (FEM) developed specifically for the needs of these problem. It is comprised of composite Lagrange-Hermite two dimensional elements defined over two dimensional space. We present some elements of the FEM and emphasise in the numerical treatment of the more complex terms. We also present novel numerical simulations and compare to in-vitro experiments of moving cells

An Extended Filament Based Lamellipodium Model Produces Various Moving Cell Shapes in the Presence of Chemotactic Signals

The Filament Based Lamellipodium Model (FBLM) is a two-phase two-dimensional continuum model, describing the dynamcis of two interacting families of locally parallel actin filaments (C.Schmeiser and D.Oelz, How do cells move? Mathematical modeling of cytoskeleton dynamics and cell migration. Cell mechanics: from single scale-based models to multiscale modeling. Chapman and Hall, 2010). It contains accounts of the filaments' bending stiffness, of adhesion to the substrate, and of cross-links connecting the two families. An extension of the model is presented with contributions from nucleation of filaments by branching, from capping, from contraction by actin-myosin interaction, and from a pressure-like repulsion between parallel filaments due to Coulomb interaction. The effect of a chemoattractant is described by a simple signal transduction model influencing the polymerization speed. Simulations with the extended model show its potential for describing various moving cell shapes, depending on the signal transduction procedure, and for predicting transients between nonmoving and moving states as well as changes of direction

Bimodality, prion aggregates infectivity and prediction of strain phenomenon

21 pagesWe consider a model for the polymerization (fragmentation) process involved in infectious prion self-replication and study both its dynamics and non-zero steady state. We address several issues. Firstly, we give conditions leading to size repartitions of PrPsc aggregates that exhibit bimodal distributions, as indicated by recent experimental studies of prion aggregates distribution. Secondly, we show stability results for this steady state for general coefficients where reduction to a system of differential equations is not possible. We use a duality method based on recent ideas developed for population models. These results underline the potential influence of the amyloid precursor production rate in promoting amyloidogenic diseases. Finally, we numerically investigate the influence of different parameters of the model on PrPsc accumulation kinetics, in the aim to study specific features of prion strains

Actin turnover maintains actin filament homeostasis during cytokinetic ring contraction

Cytokinesis in many eukaryotes involves a tension-generating actomyosin-based contractile ring. Many components of actomyosin rings turn over during contraction, although the significance of this turnover has remained enigmatic. Here, using Schizosaccharomyces japonicus, we investigate the role of turnover of actin and myosin II in its contraction. Actomyosin ring components self-organize into ∼1-µm-spaced clusters instead of undergoing full-ring contraction in the absence of continuous actin polymerization. This effect is reversed when actin filaments are stabilized. We tested the idea that the function of turnover is to ensure actin filament homeostasis in a synthetic system, in which we abolished turnover by fixing rings in cell ghosts with formaldehyde. We found that these rings contracted fully upon exogenous addition of a vertebrate myosin. We conclude that actin turnover is required to maintain actin filament homeostasis during ring contraction and that the requirement for turnover can be bypassed if homeostasis is achieved artificially

Physiological profile of world-class high altitude climbers

The functional characteristics of six world-class high-altitude mountaineers were assessed 2-12 mo after the last high-altitude climb. Each climber on one or more several occasions had reached altitudes of 8,500 m or above without supplementary O2. Static and dynamic lung volumes and right and left echocardiographic measurements were found to be within normal limits of sedentary controls (SC). Muscle fiber distribution was 70% type I, 22% type IIa, and 7% type IIb. Mean muscle fiber cross-sectional area was significantly smaller than that of SC (-15%) and of long-distance runners (LDR, -51%). The number of capillaries per unit cross-sectional area was significantly greater than that of SC (+40%). Total mitochondrial volume was not significantly different from that of SC, but its subsarcolemmal component was equal to that of LDR. Average maximal O2 consumption was 60 \ub1 6 ml\ub7kg-1\ub7min-1, which is between the values of SC and LDR. Average maximal anerobic power was 28 \ub1 2.5 W\ub7kg-1, which is equal to that of SC and 40% lower than that of competitive high jumpers. All subjects were characterized by resting hyperventilation both in normoxia and in moderate (inspired O2 partial pressure = 77 Torr) hypoxia resulting in higher oxyhemoglobin saturation levels in hypoxia. The ventilatory response to four tidal volumes of pure O2 was similar to that of SC. It is concluded that elite high-alitude climbers do not have physiological adaptations to high altitude that justify their unique performance