RESEARCH TOPICSThe focus of our research is mainly on statistical mechanics of equilibrium and non-equilibrium processes in complex systems, our specialities being stochastic processes and anomalous diffusion. We work a lot on biophysical systems, such as single particle motion in living biological cells or gene regulation. At the same time we investigate fundamental questions of statistical mechanics such as (non-)ergodicity or ageing.
Stochastic processes and anomalous diffusionSince the seminal theoretical studies of Einstein and Smoluchowski and the groundbreaking experimental works of Perrin, Nordlund, and Kappler, diffusion processes are at the core of modern statistical mechanics. While these magnificos dealt with the fundamentals of Brownian motion, in more complex systems we often observe anomalous diffusion. Our studies concern the formulation of new stochastic processes, the investigation of their properties, as well as the development of practical tools for analysis and diagnosis of experimental data. In particular, we work on ageing and weakly or ultraweakly non-ergodic systems. We use analytical tools such as the theory of stochastic processes, Lévy stable distributions and generalised central limit theorem, and fractional differential equations, as well as numerical approaches and simulations.
Molecular crowdingThe intracellular fluid (cytosol) of biological cells apart from small molecules such as water or salts is superdensely filled with biomacromolecules such as proteins or RNA molecules. The volume density occupied by such large molecules is above 35%, an enormous quantity compared to, for instance, the 3D percolation threshold of around 31%. Macromolecular crowding has immense effects on the function and kinetics of enzymes, and it changes the equilibrium constants of biochemical binding and reactions. We are interested in the physical effects and biophysical consequences of the crowding. In collaboration with experimental groups we use single particle tracking data to determine the (anomalous) stochastic processes behind the motion of individual molecules or tracer substances in living cells. We also run computer simulations to better understand the physics of crowding.
Lipid membranesBiological membranes are based on double layers of amphiphilic lipid molecules. While such lipid membranes are (complex) liquids, at sufficiently short times individual lipids perform anomalous diffusion. Based on all-atom molecular dynamics simulations we study the motin of individual lipid molecules under different biochemical conditions. We find that in all physical states lipids in a bilayer exhibit viscoelastic anomalous diffusion. The duration of the anomalous diffusion is dramatically enhanced when the disorder: addition of cholesterol molecules or proteins in the membrane extend the anomalous diffusion regime by orders of magnitude. In real systems, anomalous diffusion may last for hundreds of seconds and thus become important for the understanding of the physical and biochemical properties of membranes.
Gene regulationGene regulation is based on the location of a specific binding site on the cellular DNA by a small, diffusing protein. The fact that such transcription factors so efficiently locate their binding site is explained by the facilitated diffusion model, according to which the transcription factor combined 3D volume search with 1D motion along the DNA chain, and possibly additional mechanisms. We study facilitated diffusion both under typical dilute in vitro conditions but also under in vivo conditions of living bacterial cells. Our modelling rests on the specific introduction of the spatial aspects of the diffusional search process as well as the configuration of the DNA. Moreover we investigate the kinetics and the propagation of noise of sequential gene regulation.
DNA physicsIn its native state DNA occurs as the famed Watson-Crick double helix. However, at elevated temperature or under mechanical forcing this double helix unwinds at least partially, giving rise to unpaired, single-stranded DNA regions. We study the dynamics of the creation and closure of such DNA bubbles and their statistical behaviour as function of temperature, salt, external longitudinal as well as torsional stress. Our findings are in quantitative agreement with experimental studies of DNA bubble dynamics and equilibrium configurations measured on the level of single DNA molecules.
(Bio)Polymer translocationThe passage of a long, flexible polymer chain through a narrow pore in a membrane is a typical process necessary for the exchange between the nucleus and the remainder of biological cells, or for technological processes such as gene sequencing. Physically, this passage is accompanied by an entropic barrier when part of the polymer is fixed by the pore. We use simulations techniques and analytical models to study the dynamics of this translocation process to unravel the underlying scaling exponents. We also investigate the influence of chaperones, partially ratcheting binding proteins and the effects of heterogeneous sequences to this process.
COLLABORATORSWe currently collaborate with the following groups:
- Tobias Ambjörnsson, Lunds Universitet, Sverige
- Eli Barkai, Bar-Ilan University, Ramat Gan, Israel
- Olivier Bénichou and Raphael Voituriez, Université Pierre et Marie Curie, Paris, France
- Aleksei Chechkin, Akhiezer Institute for Theoretical Physics, Kharkov Kharkov Institute of Physics and Technology, Ukraine
- Giovanni Dietler, École Polytechnique Fédérale de Lausanne, Suisse
- Michael Lomholt, Syddansk Universitet, Odense, Danmark
- Lene Oddershede, Niels Bohr Institutet, Københavns Universitet, Danmark
- Gleb Oshanin, Université Pierre et Marie Curie, Paris, France
- Christine Selhuber-Unkel, Universität Kiel, Germany
- Ilpo Vattulainen, Tampere University of Technology (Tampereen teknillinen yliopisto), Tampere, Finland