Chromatin physics: Replacing multiple, representation-centered descriptions at discrete scales by a continuous, function-dependent self-scaled model

This commentary on the inspiring works and ideas by Langowski, Mangeol et al., Lee et al., Bundschuh and Gerland, Schiessel, Vaillant et al., Lesne and Victor, Claudet and Bednar, Fuks, Allemand et al., and Blossey, all appearing in this issue (Eur. Phys. J. E 19 (2006)), expresses our felt need of novel approaches to chromatin modeling.     

Long transients dynamics in biochemical networks

Summary  A Coupled Map Lattice, which simulates gene expression dynamics inside cells and cellular interactions on a regular lattice, shows a complex pattern of temporal behaviour. The model is represented as a network of genes interacting through their products in space and time in a lattice of genetically identical cells. Despite the fact that the system is described through a step function that imposes a simple repertoire of constant or oscillatory steady states, the dynamics over the lattice are extremely complex. One of the main feature of the asymptotic dynamics is the appearance of long transients in certain regions of parameter space, before the attainment of the final stable attractor. These dynamics, that can grow linearly or exponentially with lattice size, can become the only dynamics computationally observable. The study of the global dynamics-i.e. the average value of the variable over the lattice-shows a qualitative different behaviour depending on the region of the parameter space observed. In the case of the linear transient-growth region the system shows an average that falls quickly on a periodic attractor. In the exponential region values of the average quantities show a behaviour that has stochastic properties. At the boundary of these two regimes the system has an average that shows a complex behaviour before attainment of the final attractor. The possible implications of these results for the study of the dynamical aspects of gene regulation, biochemical pathways and in signal transduction in experimental systems are discussed. This work has been partially supported by CNR grant No. 95.01751.CT14 “Studio analitico della dinamica della regolazione genica e della morfogenesi#x201C;, and by funds from the National Ministry of Public Health. FB and RL would like to thank I.S.I., Torino, for the kind hospitality during the workshop of the EEC Network “Complexity and Chaos#x201D;, contract No. ERBCHRX-CT940546, in 1995 and 1996, during which part of this research has been done.     

A simple atomistic model for the simulation of the gel phase of lipid bilayers

In this paper we present the results of a large-scale numerical investigation of structural properties of a model of cell membrane, simulated as a bilayer of flexible molecules in vacuum. The study was performed by carrying out extensive Molecular Dynamics simulations, in the (NVE) micro-canonical ensemble, of two systems of different sizes ( 2×32 and 2×256 molecules), over a fairly large set of temperatures and densities, using parallel platforms and more standard serial computers. Depending on the dimension of the system, the dynamics was followed for physical times that go from few hundred picoseconds for the largest system to 5-10 nanoseconds for the smallest one. We find that the bilayer remains stable even in the absence of water and neglecting Coulomb interactions in the whole range of temperatures and densities we have investigated. The extension of the region of physical parameters that we have explored has allowed us to study significant points in the phase diagram of the bilayer and to expose marked structural changes as density and temperature are varied, which are interpreted as the system passing from a crystal to a gel phase. Received 6 July 2000 and Received in final form 28 December 2000     

Studying the emergence of invasiveness in tumours using game theory

Tumour cells have to acquire a number of capabilities if a neoplasm is to become a cancer. One of these key capabilities is increased motility which is needed for invasion of other tissues and metastasis. This paper presents a qualitative mathematical model based on game theory and computer simulations using cellular automata. With this model we study the circumstances under which mutations that confer increased motility to cells can spread through a tumour made of rapidly proliferating cells. The analysis suggests therapies that could help prevent the progression towards malignancy and invasiveness of benign tumours.     

Photoemission and coincidence studies on gas-phase molecules

This article describes Young’s double-slit experiment using high-energy core-level photoemission from N₂ molecules and experimental identification of interatomic Coulombic decay in Ar₂ dimers after Auger decay using k-resolved electron–ion–ion coincidence spectroscopy, aiming to illustrate the leading edge of gas-phase experiments using synchrotron radiation.     

Collective alignment of polar filaments by molecular motors

We study the alignment of polar biofilaments, such as microtubules and actin, subject to the action of multiple molecular motors attached simultaneously to more than one filament. Focusing on a paradigm model of only two filaments interacting with multiple motors, we were able to investigate in detail the alignment dynamics. While almost no alignment occurs in the case of a single motor, the filaments become rapidly aligned due to the collective action of the motors. Our analysis shows that the alignment time is governed by the number of bound motors and the magnitude of the motors’ stepping fluctuations. We predict that the time scale of alignment is in the order of seconds, much faster than that reported for passive crosslink-induced bundling. In vitro experiments on the alignment of microtubules by multiple-motor covered beads are in qualitative agreement. We also discuss another mode of fast alignment of filaments, namely the cooperation between motors and passive crosslinks.     

On the chaining dynamics of inclusions in SmC* free standing films

A simplified model of an inclusion represented by (+1)-wedge disclination and an accompanying hyperbolic defect ((−1)-wedge disclination) in smectic C* free standing films is used to describe the early stage of the ordering process of inclusions into chains. The elastic interaction between inclusions and their associated hyperbolic defects is used to discuss the dynamics observed experimentally during the inclusion chaining when inclusions are at distances much larger than their radii. This work was also supported by Grant No. 202/02/0840 of the Grant Agency of the Czech Republic and by the research project AV0Z1-010-914.     

Localization and delocalization of energy in a Peyrard-Bishop chain

This paper studies energy localization conditions in lattices of the type proposed by Peyrard and Bishop. Homogeneous and inhomogeneous lattices are analyzed and the role of interfaces in the latter is emphasized. Simulations allowed us to identify critical energy values for the existence of localization. After a certain energy value, it is possible to observe the loss of energy localization along the chain.     

Instabilities in a two-dimensional polar-filament-motor system

The dynamical interaction between filaments and motor proteins is known for their propensity to self-organize into spatio-temporal patterns. Since the filaments are polar in the sense that motors define a direction of motion on them, the system can display a spatially homogeneous polar-filament orientation. We show that the latter anisotropic state itself may become unstable with respect to inhomogeneous fluctuations. This scenario shares similarities with instabilities in planarly aligned nematic liquid crystals: in both cases the wave vector of the instability may be oriented either parallel or oblique to the polarity axis. However, the encountered instabilities here are long-wave instead of short-wave and the destabilizing modes are drifting ones due to the polar symmetry. Additionally a nonpropagating transverse instability is possible. The stability diagrams related to the various wave vector orientations relative to the polarity axis are determined and discussed for a specific model of motor-filament interactions.     

Magnet design and beam dynamics in computed fields for the DC-350 cyclotron

The DC-350 is an isochronous cyclotron designed in the Flerov Laboratory of Nuclear Reaction (FLNR). It is intended for accelerating ions with a mass-to-charge ratio A/Z within an interval of 5–10 and with an energy of 3–12 MeV/u at the extraction radius. These ion beams will be used in nuclear and applied physics experiments. The paper describes the results of a 3D magnet simulation. The cyclotron magnet and IM90 analiziting-bend magnet of the axial injection channel are studied here. The influence of correction coils on the cyclotron magnet is calculated. All magnet fields were calculated by MERMAID 3D code [1]. The text was submitted by the authors in English.     

Beam dynamics study in the C235 cyclotron for proton therapy

A study of the beam dynamics in the C235 (T06) cyclotron made for proton therapy is presented. Results of the computer simulations of the particle motion in the measured magnetic field are given. A study of the resonance influence on the acceleration process was carried out. The corresponding tolerances on the magnetic field imperfections and transverse beam parameters were defined using these simulations. The text was submitted by the authors in English.     

Simulating 3D intense beam dynamics simulation using the moments method

The program of the 3D intense beam dynamic simulation based on the moments method is presented. The text was submitted by the authors in English.     

Propagation of terawatt laser pulses in the air

One of the problems when increasing the intensity of a femtosecond laser pulse is the propagation of the beam. As the intensity increases nonlinear effects begin to play a significant role. When arriving to the terawatt domain, nonlinear effects and filamentation give rise to a new phenomenology in the propagation. The aim of this paper is to analyze new possibilities to control the beam shape to Taylor the interaction of the beam with the target at large distances.     

Electrostatic and electrokinetic contributions to the elastic moduli of a driven membrane

We discuss the electrostatic contribution to the elastic moduli of a cell or artificial membrane placed in an electrolyte and driven by a DC electric field. The field drives ion currents across the membrane, through specific channels, pumps or natural pores. In steady state, charges accumulate in the Debye layers close to the membrane, modifying the membrane elastic moduli. We first study a model of a membrane of zero thickness, later generalizing this treatment to allow for a finite thickness and finite dielectric constant. Our results clarify and extend the results presented by D. Lacoste, M. Cosentino Lagomarsino, and J.F. Joanny (EPL 77, 18006 (2007)), by providing a physical explanation for a destabilizing term proportional to k _⊥ ³ in the fluctuation spectrum, which we relate to a nonlinear (E²) electrokinetic effect called induced-charge electro-osmosis (ICEO). Recent studies of ICEO have focused on electrodes and polarizable particles, where an applied bulk field is perturbed by capacitive charging of the double layer and drives the flow along the field axis toward surface protrusions; in contrast, we predict “reverse” ICEO flows around driven membranes, due to curvature-induced tangential fields within a nonequilibrium double layer, which hydrodynamically enhance protrusions. We also consider the effect of incorporating the dynamics of a spatially dependent concentration field for the ion channels.     

The Static Modes: An alternative approach for the treatment of macro- and bio-molecular induced-fit flexibility

We present a new competitive method for the atomic scale treatment of macromolecular flexibility called Static Mode method. This method is based on the “induced-fit” concept, i.e. it maps the intrinsic deformations of a macromolecule subject to diverse external excitations. The algorithm makes it possible to obtain a set of deformations, each one corresponding to a specific interaction on a specific molecular site, in terms of force constants contained in the energy model. In this frame, the docking problem can be expressed in terms of interaction sites between the two molecules, the molecular deformations being extracted from the pre-calculated Static Modes of each molecule. Some preliminary basic examples aimed at illustrating potential applications where macro- or bio-molecular flexibility is of key importance are given: flexibility inducing conformational changes in the case of furanose ring and flexibility for the characterization, including allostery, of poly(N-isopropylacrylamide)(P-NIPAM) active sites. We also discuss how this procedure allows “induced-fit” flexible molecular docking, beyond state-of-the-art semi-rigid methods.