Publications

Immunophysics

Publications Immunophysics Division

2016

Superdiffusive Dispersals Impart the Geometry of Underlying Random Walks

Vasily Zaburdaev, I. Fouxon, S. Denisov, E. Barkai

Physical Review Letters 117 (27) 270601 (2016) | Journal

It is recognized now that a variety of real-life phenomena ranging from diffusion of cold atoms to the motion of humans exhibit dispersal faster than normal diffusion. Levy walks is a model that excelled in describing such superdiffusive behaviors albeit in one dimension. Here we show that, in contrast to standard random walks, the microscopic geometry of planar superdiffusive Levy walks is imprinted in the asymptotic distribution of the walkers. The geometry of the underlying walk can be inferred from trajectories of the walkers by calculating the analogue of the Pearson coefficient.

Superdiffusive Dispersals Impart the Geometry of Underlying Random Walks

Vasily Zaburdaev, I. Fouxon, S. Denisov, E. Barkai

Physical Review Letters 117 (27) 270601 (2016) | Journal

It is recognized now that a variety of real-life phenomena ranging from diffusion of cold atoms to the motion of humans exhibit dispersal faster than normal diffusion. Levy walks is a model that excelled in describing such superdiffusive behaviors albeit in one dimension. Here we show that, in contrast to standard random walks, the microscopic geometry of planar superdiffusive Levy walks is imprinted in the asymptotic distribution of the walkers. The geometry of the underlying walk can be inferred from trajectories of the walkers by calculating the analogue of the Pearson coefficient.

Nucleosomal arrangement affects single-molecule transcription dynamics

Veronika Fitz, Jaeoh Shin, Christoph Ehrlich, Lucas Farnung, Patrick Cramer, Vasily Zaburdaev, Stephan W. Grill

Proceedings of the National Academy of Sciences of the United States of America 113 (45) 12733-12738 (2016) | Journal

In eukaryotes, gene expression depends on chromatin organization. However, how chromatin affects the transcription dynamics of individual RNA polymerases has remained elusive. Here, we use dual trap optical tweezers to study single yeast RNA polymerase II (Pol II) molecules transcribing along a DNA template with two nucleosomes. The slowdown and the changes in pausing behavior within the nucleosomal region allow us to determine a drift coefficient,., which characterizes the ability of the enzyme to recover from a nucleosomal backtrack. Notably, chi can be used to predict the probability to pass the first nucleosome. Importantly, the presence of a second nucleosome changes chi in a manner that depends on the spacing between the two nucleosomes, as well as on their rotational arrangement on the helical DNA molecule. Our results indicate that the ability of Pol II to pass the first nucleosome is increased when the next nucleosome is turned away from the first one to face the opposite side of the DNA template. These findings help to rationalize how chromatin arrangement affects Pol II transcription dynamics.

Nucleosomal arrangement affects single-molecule transcription dynamics

Veronika Fitz, Jaeoh Shin, Christoph Ehrlich, Lucas Farnung, Patrick Cramer, Vasily Zaburdaev, Stephan W. Grill

Proceedings of the National Academy of Sciences of the United States of America 113 (45) 12733-12738 (2016) | Journal

In eukaryotes, gene expression depends on chromatin organization. However, how chromatin affects the transcription dynamics of individual RNA polymerases has remained elusive. Here, we use dual trap optical tweezers to study single yeast RNA polymerase II (Pol II) molecules transcribing along a DNA template with two nucleosomes. The slowdown and the changes in pausing behavior within the nucleosomal region allow us to determine a drift coefficient,., which characterizes the ability of the enzyme to recover from a nucleosomal backtrack. Notably, chi can be used to predict the probability to pass the first nucleosome. Importantly, the presence of a second nucleosome changes chi in a manner that depends on the spacing between the two nucleosomes, as well as on their rotational arrangement on the helical DNA molecule. Our results indicate that the ability of Pol II to pass the first nucleosome is increased when the next nucleosome is turned away from the first one to face the opposite side of the DNA template. These findings help to rationalize how chromatin arrangement affects Pol II transcription dynamics.

Reaction front propagation of actin polymerization in a comb-reaction system

A. Iomin, Vasily Zaburdaev, T. Pfohl

Chaos Solitons & Fractals 92 115-122 (2016) | Journal

We develop a theoretical model of anomalous transport with polymerization-reaction dynamics. We are motivated by the experimental problem of actin polymerization occurring in a microfluidic device with a comb-like geometry. Depending on the concentration of reagents, two limiting regimes for the propagation of reaction are recovered: the failure of the reaction front propagation and a finite speed of the reaction front corresponding to the Fisher-Kolmogorov-Petrovskii-Piscounov (FKPP) at the long time asymptotic regime. To predict the relevance of these regimes we obtain an explicit expression for the transient time as a function of geometry and parameters of the experimental setup. Explicit analytical expressions of the reaction front velocity are obtained as functions of the experimental setup. (C) 2016 Elsevier Ltd. All rights reserved.

Reaction front propagation of actin polymerization in a comb-reaction system

Alexander Iomin, Vasily Zaburdaev, T. Pfohl

Chaos, Solitons and Fractals 92 115-122 (2016) | Journal

We develop a theoretical model of anomalous transport with polymerization-reaction dynamics. We are motivated by the experimental problem of actin polymerization occurring in a microfluidic device with a comb-like geometry. Depending on the concentration of reagents, two limiting regimes for the propagation of reaction are recovered: the failure of the reaction front propagation and a finite speed of the reaction front corresponding to the Fisher-Kolmogorov-Petrovskii-Piscounov (FKPP) at the long time asymptotic regime. To predict the relevance of these regimes we obtain an explicit expression for the transient time as a function of geometry and parameters of the experimental setup. Explicit analytical expressions of the reaction front velocity are obtained as functions of the experimental setup. (C) 2016 Elsevier Ltd. All rights reserved.

A pH-driven transition of the cytoplasm from a fluid- to a solid-like state promotes entry into dormancy

Matthias Christoph Munder, Daniel Midtvedt, Titus Franzmann, Elisabeth Nueske, Oliver Otto, Maik Herbig, Elke Ulbricht, Paul Mueller, Anna Taubenberger, et al.

eLife 5 e09347 (2016) | Journal

Cells can enter into a dormant state when faced with unfavorable conditions. However, how cells enter into and recover from this state is still poorly understood. Here, we study dormancy in different eukaryotic organisms and find it to be associated with a significant decrease in the mobility of organelles and foreign tracer particles. We show that this reduced mobility is caused by an influx of protons and a marked acidification of the cytoplasm, which leads to widespread macromolecular assembly of proteins and triggers a transition of the cytoplasm to a solid-like state with increased mechanical stability. We further demonstrate that this transition is required for cellular survival under conditions of starvation. Our findings have broad implications for understanding alternative physiological states, such as quiescence and dormancy, and create a new view of the cytoplasm as an adaptable fluid that can reversibly transition into a protective solid-like state.

Subnuclear Spatial Structuring of Chromatin and Polymerase II during Transcription Activation of the Zebrafish Zygotic Genome

Lennart Hilbert, Vasily Zaburdaev, Nadine Vastenhouw

Biophysical Journal 110 (3) 232A-233A (2016) | Journal

The relevance of spatial organization of chromatin to regulation of transcription is increasingly recognized [1]. Conversely, it was recently suggested that the level of general transcription activity affects subnuclear chromatin distribution [2]. Here, we ask how a general increase in transcription by polymerase II changes subnuclear chromatin distribution. Specifically, we used the transition of early zebrafish embryos from transcription quiescence to fully established transcription (Zygotic Genome Activation - ZGA) as a naturally occurring example of transcription level increase. General transcription activity occurs only following ZGA, i.e. 10 synchronous cell divisions after initial fertilization (three hours post fertilization). To make subnuclear distribution changes during ZGA accessible to super-resolution microscopy, we developed a dissociated cell culture protocol. Zebrafish embryos were dissociated at the 128-cell stage (three cell divisions before ZGA). Cultured cells developed transcription activity and morphological hallmarks of ZGA, confirming occurrence of native ZGA. We obtained preliminary results by wide-field fluorescence microscopy. Using fluorescently labeled histone proteins, which spontaneously bind DNA, we visualized a fine-grained chromatin structure in post-ZGA interphase nuclei in vivo. Utilizing antibody fragments (Fabs), we detected agglomerations of transcribing polymerase II in vivo. These agglomerations appeared as micron-sized, approximately spherical “transcription hot spots”. Few large transcription hot spots occurred at the 256-cell stage; in consecutive cell cycles more and smaller spots appeared. Any distinct signal of transcribing polymerase II disappeared during cell divisions, when no transcription occurs, thus confirming specificity of Fab-based detection of actively transcribing polymerase II. In the future, we will employ super-resolution microscopy to resolve the fine structure of chromatin and transcription hot spots in vivo throughout native zebrafish ZGA. [1] Gavrilov and Razin, Molecular Biology, 2015. [2] Popken et al., Nucleus, 2015.

A pH-driven transition of the cytoplasm from a fluid- to a solid-like state promotes entry into dormancy

Matthias Christoph Munder, Daniel Midtvedt, Titus Franzmann, Elisabeth Nueske, Oliver Otto, Maik Herbig, Elke Ulbricht, Paul Mueller, Anna Taubenberger, et al.

eLife 5 e09347 (2016) | Journal

Cells can enter into a dormant state when faced with unfavorable conditions. However, how cells enter into and recover from this state is still poorly understood. Here, we study dormancy in different eukaryotic organisms and find it to be associated with a significant decrease in the mobility of organelles and foreign tracer particles. We show that this reduced mobility is caused by an influx of protons and a marked acidification of the cytoplasm, which leads to widespread macromolecular assembly of proteins and triggers a transition of the cytoplasm to a solid-like state with increased mechanical stability. We further demonstrate that this transition is required for cellular survival under conditions of starvation. Our findings have broad implications for understanding alternative physiological states, such as quiescence and dormancy, and create a new view of the cytoplasm as an adaptable fluid that can reversibly transition into a protective solid-like state.

Contact

Immunophysics Division
Prof. Vasily Zaburdaev
Principal Investigator

Max-Planck-Zentrum für Physik und Medizin
Kussmaulallee 2
Room 02.116
91054 Erlangen, Germany
+49 9131 8284 102

vasily.zaburdaev@mpzpm.mpg.de


Silke Besold

Secretary

Friedrich-Alexander-Universität Erlangen-Nürnberg
Chair of Mathematics in Life Sciences
Kussmaulallee 2
Room 02.122
91054 Erlangen, Germany
+49 9131 8284 104

silke.besold@fau.de

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Graduate Program