Igor M. Kulić

The role of microtubule movement in bidirectional organelle transport

We study the role of microtubule movement in bidirectional organelle transport in Drosophila S2 cells and show that EGFP-tagged peroxisomes in cells serve as sensitive probes of motor induced, noisy cytoskeletal motions. Multiple peroxisomes move in unison over large time windows and show correlations with microtubule tip positions, indicating rapid microtubule fluctuations in the longitudinal direction. We report the first high-resolution measurement of longitudinal microtubule fluctuations performed by tracing such pairs of co-moving peroxisomes. The resulting picture shows that motor-dependent longitudinal microtubule oscillations contribute significantly to cargo movement along microtubules. Thus, contrary to the conventional view, organelle transport cannot be described solely in terms of cargo movement along stationary microtubule tracks, but instead includes a strong contribution from the movement of the tracks.

DNA spools under tension.

DNA spools, structures in which DNA is wrapped and helically coiled onto itself or onto a protein core, are ubiquitous in nature. We develop a general theory describing the nonequilibrium behavior of DNA spools under linear tension. Two puzzling and seemingly unrelated recent experimental findings, the sudden quantized unwrapping of nucleosomes and that of DNA toroidal condensates under tension, are theoretically explained and shown to be of the same origin. The study provides new insights into nucleosome and chromatin fiber stability and dynamics.

Nucleosome repositioning via loop formation.

Active (catalyzed) and passive (intrinsic) nucleosome repositioning is known to be a crucial event during the transcriptional activation of certain eukaryotic genes. Here we consider theoretically the intrinsic mechanism and study in detail the energetics and dynamics of DNA-loop-mediated nucleosome repositioning, as previously proposed by earlier works. The surprising outcome of the present study is the inherent nonlocality of nucleosome motion within this model-being a direct physical consequence of the loop mechanism. On long enough DNA templates the longer jumps dominate over the previously predicted local motion, a fact that contrasts simple diffusive mechanisms considered before. The possible experimental outcome resulting from the considered mechanism is predicted, discussed, and compared to existing experimental findings.

Apparent persistence length renormalization of bent DNA.

We derive the single molecule equation of state (force-extension relation) for DNA molecules bearing sliding loops and deflection defects. Analytical results are obtained in the large force limit by employing an analogy with instantons in quantum mechanical tunneling problems. The results reveal a remarkable feature of sliding loops--an apparent strong reduction of the persistence length. We generalize these results to several other experimentally interesting situations ranging from rigid DNA-protein loops to the problem of anchoring deflections in atomic force microscopy stretching of semiflexible polymers. Expressions relating the force-extension measurements to the underlying loop or boundary deflection geometry are provided and applied to the case of the gal repressor dimer protein. The theoretical predictions are complemented and quantitatively confirmed by molecular dynamics simulations.

Buckling of stiff polymers: influence of thermal fluctuations.

Marc Emanuel, Hervé Mohrbach, Mehmet Sayar, Helmut Schiessel, and Igor M. Kulić Instituut-Lorentz, Universiteit Leiden, Postbus 9506, 2300 RA Leiden, The Netherlands Institut de Physique, Université Paul Verlaine-Metz, LPMC, CPMB1-FR CNRS 2843, 1 boulevard Arago, 57078 Metz, France Koc University, College of Engineering, 34450 Sariyer, Istanbul, Turkey School of Engineering and Applied Sciences, Harvard University, Cambridge, Massachusetts 02138, USA

Twirling DNA rings Swimming nanomotors ready for a kickstart

We propose a rotary DNA nanomachine that shows a continuous rotation with a frequency of around 100 Hz. This motor consists of a DNA ring whose elastic features are tuned such that it can be externally driven via a periodic temperature change. As a result, the ring propels itself through the fluid with a speed up to tens of nanometers per second.

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.

Brownian dynamics of a microswimmer

Abstract.We report on dynamic properties of a simple model microswimmer composed of three spheres and propelling itself in a viscous fluid by spinning motion of the spheres under zero net torque constraint. At a fixed temperature and increasing the spinning frequency, the swimmer demonstrates a transition from dissipation-dominated to a pumping-dominated motion regime characterized by negative effective friction coefficient. In the limit of high frequencies, the diffusion of the swimmer can be described by a model of an active particle with constant velocity.

Cooperative lattice dynamics and anomalous fluctuations of microtubules

Microtubules have been in the focus of biophysical research for several decades. However, the confusing and mutually contradictory results regarding their elasticity and fluctuations have cast doubt on their present understanding. In this paper, we present the empirical evidence for the existence of discrete guanosine diphosphate (GDP)–tubulin fluctuations between a curved and a straight configuration at room temperature as well as for conformational tubulin cooperativity. Guided by a number of experimental findings, we build the case for a novel microtubule model, with the principal result that microtubules can spontaneously form micron-sized cooperative helical states with unique elastic and dynamic features. The polymorphic dynamics of the microtubule lattice resulting from the tubulin bistability quantitatively explains several experimental puzzles, including anomalous scaling of dynamic fluctuations of grafted microtubules, their apparent length–stiffness relation, and their remarkable curved–helical appearance in general. We point out that the multistability and cooperative switching of tubulin dimers could participate in important cellular processes, and could in particular lead to efficient mechanochemical signaling along single microtubules.

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.