Falko Ziebert

Model for self-polarization and motility of keratocyte fragments

Computational modelling of cell motility on substrates is a formidable challenge; regulatory pathways are intertwined and forces that influence cell motion are not fully quantified. Additional challenges arise from the need to describe a moving deformable cell boundary. Here, we present a simple mathematical model coupling cell shape dynamics, treated by the phase-field approach, to a vector field describing the mean orientation (polarization) of the actin filament network. The model successfully reproduces the primary phenomenology of cell motility: discontinuous onset of motion, diversity of cell shapes and shape oscillations. The results are in qualitative agreement with recent experiments on motility of keratocyte cells and cell fragments. The asymmetry of the shapes is captured to a large extent in this simple model, which may prove useful for the interpretation of experiments.

Effects of Adhesion Dynamics and Substrate Compliance on the Shape and Motility of Crawling Cells

Computational modeling of eukaryotic cells moving on substrates is an extraordinarily complex task: many physical processes, such as actin polymerization, action of motors, formation of adhesive contacts concomitant with both substrate deformation and recruitment of actin etc., as well as regulatory pathways are intertwined. Moreover, highly nontrivial cell responses emerge when the substrate becomes deformable and/or heterogeneous. Here we extended a computational model for motile cell fragments, based on an earlier developed phase field approach, to account for explicit dynamics of adhesion site formation, as well as for substrate compliance via an effective elastic spring. Our model displays steady motion vs. stick-slip transitions with concomitant shape oscillations as a function of the actin protrusion rate, the substrate stiffness, and the rates of adhesion. Implementing a step in the substrate’s elastic modulus, as well as periodic patterned surfaces exemplified by alternating stripes of high and low adhesiveness, we were able to reproduce the correct motility modes and shape phenomenology found experimentally. We also predict the following nontrivial behavior: the direction of motion of cells can switch from parallel to perpendicular to the stripes as a function of both the adhesion strength and the width ratio of adhesive to non-adhesive stripes.

Nonlinear competition between asters and stripes in filament-motor systems

Abstract.A model for polar filaments interacting via molecular motor complexes is investigated which exhibits bifurcations to spatial patterns. It is shown that the homogeneous distribution of filaments, such as actin or microtubules, may become either unstable with respect to an orientational instability of a finite wave number or with respect to modulations of the filament density, where long-wavelength modes are amplified as well. Above threshold nonlinear interactions select either stripe patterns or periodic asters. The existence and stability ranges of each pattern close to threshold are predicted in terms of a weakly nonlinear perturbation analysis, which is confirmed by numerical simulations of the basic model equations. The two relevant parameters determining the bifurcation scenario of the model can be related to the concentrations of the active molecular motors and of the filaments, respectively, which both could be easily regulated by the cell.

Effective zero-thickness model for a conductive membrane driven by an electric field

The behavior of a conductive membrane in a static (dc) electric field is investigated theoretically. An effective zero-thickness model is constructed based on a Robin-type boundary condition for the electric potential at the membrane, originally developed for electrochemical systems. Within such a framework, corrections to the elastic moduli of the membrane are obtained, which arise from charge accumulation in the Debye layers due to capacitive effects and electric currents through the membrane and can lead to an undulation instability of the membrane. The fluid flow surrounding the membrane is also calculated, which clarifies issues regarding these flows sharing many similarities with flows produced by induced charge electro-osmosis (ICEO). Nonequilibrium steady states of the membrane and of the fluid can be effectively described by this method. It is both simpler, due to the zero thickness approximation which is widely used in the literature on fluid membranes, and more general than previous approaches. The predictions of this model are compared to recent experiments on supported membranes in an electric field.

Effects of cross-links on motor-mediated filament organization

Cross-links and molecular motors play an important role in the organization of cytoskeletal filament networks. Here, we incorporate the effect of cross-links into our model of polar motor-filament organization (Aranson and Tsimring 2005 Phys. Rev. E 71 050901), through suppressing the relative sliding of filaments in the course of motor-mediated alignment. We show that this modification leads to a nontrivial macroscopic behavior, namely the oriented state exhibits a transverse instability in contrast to the isotropic instability that occurs without cross-links. This transverse instability leads to the formation of dense extended bundles of oriented filaments, similar to the recently observed structures in actomyosin. This model can be also applied to situations with two oppositely directed motor species or motors with different processing speeds.

Why microtubules run in circles: mechanical hysteresis of the tubulin lattice.

The fate of every eukaryotic cell subtly relies on the exceptional mechanical properties of microtubules. Despite significant efforts, understanding their unusual mechanics remains elusive. One persistent, unresolved mystery is the formation of long-lived arcs and rings, e.g., in kinesin-driven gliding assays. To elucidate their physical origin we develop a model of the inner workings of the microtubules lattice, based on recent experimental evidence for a conformational switch of the tubulin dimer. We show that the microtubule lattice itself coexists in discrete polymorphic states. Metastable curved states can be induced via a mechanical hysteresis involving torques and forces typical of few molecular motors acting in unison, in agreement with the observations.

Simple view on fingering instability of debonding soft elastic adhesives.

We study the crack-front fingering instability of an elastic adhesive tape that is peeled off a solid substrate. Our analysis is based on an energy approach using fracture mechanics and scaling laws and provides simple physical explanations for (i) the fact that the wavelength depends only on the thickness of the adhesive film and (ii) the threshold of the instability, and (iii) additionally estimates the characteristic size of the fingers. The scaling laws for these three observables are in agreement with existing experimental data.

A Poisson–Boltzmann approach for a lipid membrane in an electric field

The behavior of a non-conductive quasi-planar lipid membrane in an electrolyte and in a static (dc) electric field is investigated theoretically in the nonlinear (Poisson–Boltzmann) regime. Electrostatic effects due to charges in the membrane lipids and in the double layers lead to corrections to the membrane elastic moduli, which are analyzed here. We show that, especially in the low salt limit, (i) the electrostatic contribution to the membranes surface tension due to the Debye layers crosses over from a quadratic behavior in the externally applied voltage to a linear voltage regime, and (ii) the contribution to the membranes bending modulus due to the Debye layers saturates for high voltages. Nevertheless, the membrane undulation instability due to an effectively negative surface tension predicted by the linear Debye–Huckel theory is shown to persist in the nonlinear, high-voltage regime.

Chapter three – A Planar Lipid Bilayer in an Electric Field: Membrane Instability, Flow Field, and Electrical Impedance

Abstract For many biotechnological applications it would be useful to better understand the effects produced by electric fields on lipid membranes. This review discusses several aspects of the electrostatic properties of a planar lipid membrane with its surrounding electrolyte in a normal DC or AC electric field. In the planar geometry, the analysis of electrokinetic equations can be carried out quite far, allowing to characterize analytically the steady state and the dynamics of the charge accumulation in the Debye layers, which results from the application of the electric field. For a conductive membrane in an applied DC electric field, we characterize the corrections to the elastic moduli, the appearance of a membrane undulation instability and the associated flows which are built up near the membrane. For a membrane in an applied AC electric field, we analytically derive the impedance from the underlying electrokinetic equations. We discuss different relevant effects due to the membrane conductivity or due to the bulk diffusion coefficients of the ions. Of particular interest is the case where the membrane has selective conductivity for only one type of ion. These results, and future extensions thereof, should be useful for the interpretation of impedance spectroscopy data used to characterize, for example, ion channels embedded in planar bilayers.For many biotechnological applications it would be useful to better understand the effects produced by electric fields on lipid membranes. This review discusses several aspects of the electrostatic properties of a planar lipid membrane with its surrounding electrolyte in a normal DC or AC electric field. In the planar geometry, the analysis of electrokinetic equations can be carried out quite far, allowing to characterize analytically the steady state and the dynamics of the charge accumulation in the Debye layers, which results from the application of the electric field. For a conductive membrane in an applied DC electric field, we characterize the corrections to the elastic moduli, the appearance of a membrane undulation instability and the associated flows which are built up near the membrane. For a membrane in an applied AC electric field, we analytically derive the impedance from the underlying electrokinetic equations. We discuss different relevant effects due to the membrane conductivity or due to the bulk diffusion coefficients of the ions. Of particular interest is the case where the membrane has selective conductivity for only one type of ion. These results, and future extensions thereof, should be useful for the interpretation of impedance spectroscopy data used to characterize, for example, ion channels embedded in planar bilayers.

Semiflexible Chains at Surfaces: Worm-Like Chains and beyond

We give an extended review of recent numerical and analytical studies on semiflexible chains near surfaces undertaken at Institut Charles Sadron (sometimes in collaboration) with a focus on static properties. The statistical physics of thin confined layers, strict two-dimensional (2D) layers and adsorption layers (both at equilibrium with the dilute bath and from irreversible chemisorption) are discussed for the well-known worm-like-chain (WLC) model. There is mounting evidence that biofilaments (except stable d-DNA) are not fully described by the WLC model. A number of augmented models, like the (super) helical WLC model, the polymorphic model of microtubules (MT) and a model with (strongly) nonlinear flexural elasticity are presented, and some aspects of their surface behavior are analyzed. In many cases, we use approaches different from those in our previous work, give additional results and try to adopt a more general point of view with the hope to shed some light on this complex field.