SearcharxivSearch

arXiv subjects

Helmut Schiessel

Publications and source records attributed to Helmut Schiessel.

17 recordsLinked to original sources

Roadmap for Condensates in Cell Biology

Biomolecular condensates govern essential cellular processes yet elude description by traditional equilibrium models. This roadmap, distilled from structured discussions at a workshop and reflecting the consensus of its participants, clarifies key concepts for researchers, funding bodies, and journals. After unifying terminology that often separates disciplines, we outline the core physics of condensate formation, review their biological roles, and identify outstanding challenges in nonequilibrium theory, multiscale simulation, and quantitative in-cell measurements. We close with a forward-looking outlook to guide coordinated efforts toward predictive, experimentally anchored understanding and control of biomolecular condensates.

physics.bio-ph

A self-organised liquid reaction container for cellular memory

Epigenetic inheritance during cell division is essential for preserving cell identity by stabilizing the overall chromatin organisation. Heterochromatin,the condensed and transcriptionally silent fraction of chromatin,is marked by specific epigenetic modifications that are diluted during each cell division. Here we build a physical model,based on the formation of a biomolecular condensate,a liquid 'droplet',that promotes the restoration of epigenetic marks. Heterochromatin facilitates the droplet formation via polymer-assisted condensation(PAC). The resulting condensate serves as a reaction chamber to reconstruct the lost epigenetic marks. We incorporate the enzymatic reactions into a particle-based simulation and monitor the progress of the epigenetic markers through an in silico analogue of the cell cycle. We demonstrate that the proposed mechanism is robust and stabilizes the heterochromatin domains over many cell generations. This mechanism and variations thereof might be at work for other epigenetic marks as well.

physics.bio-ph

Statistical Mechanics of Multiplectoneme Phases in DNA

A stretched DNA molecule which is also under- or overwound, undergoes a buckling transition forming intertwined looped domains called plectonemes. Here we develop a simple theory that extends the two-phase model of stretched supercoiled DNA, allowing for the coexistence of multiple plectonemic domains by including positional and length distribution entropies. Such a multiplectoneme phase is favored in long DNA molecules in which the gain of positional entropy compensates for the cost of nucleating a plectoneme along a stretched DNA segment. Despite its simplicity, the developed theory is shown to be in excellent agreement with Monte Carlo simulations of the twistable wormlike chain model. The theory predicts more plectonemes than experimentally observed, which we attribute to the limited resolution of experimental data. Since plectonemes are detected through fluorescence signals, those shorter than the observable threshold are likely missed.

cond-mat.soft

Systematic Coarse-Graining of Sequence-Dependent Structure and Elasticity of Double-Stranded DNA

Coarse-grained models have played an important role in the study of the behavior of DNA at length scales beyond a few hundred base pairs. Traditionally, these models have relied on structurally featureless and sequence-independent approaches, such as the twistable worm-like chain. However, research over the past decade has illuminated the substantial impact of DNA sequence even at the kilo-base pair scale. Several robust sequence-dependent models have emerged, capturing intricacies at the base pair-step level. Here we introduce an analytical framework for coarse-graining such models to the 2 to 40-base pair scale while preserving essential structural and dynamical features. These faithful coarse-grained parametrizations enable efficient sampling of large molecules. Rather than providing a fully parametrized model, we present the methodology and software necessary for mapping any base pair-step model to the desired level of coarse-graining. Finally, we provide application examples of our method, including estimates of the persistence length and effective torsional stiffness of DNA in a setup mimicking a freely orbiting tweezer, as well as simulations of intrinsically helical DNA.

cond-mat.soft

Unwinding Dynamics of a Helically Wrapped Polymer

We study the rotational dynamics of a flexible polymer initially wrapped around a rigid rod and unwinding from it. This dynamics is of interest in several problems in biology and constitutes a fundamental instance of polymer relaxation from a state of minimal entropy. We investigate the dynamics of several quantities such as the total and local winding angles and metric quantities. The results of simulations performed in two and three dimensions, with and without self-avoidance, are explained by a theory based on scaling arguments and on a balance between frictional and entropic forces. The early stage of the dynamics is particularly rich, being characterized by three coexisting phases.

cond-mat.soft

Multi-plectoneme phase of double-stranded DNA under torsion

We use the worm-like chain model to study supercoiling of DNA under tension and torque. The model reproduces experimental data for a broad range of forces, salt concentrations and contour lengths. We find a plane of first order phase transitions ending in a smeared out line of critical points, the multi-plectoneme phase, which is characterized by a fast twist mediated diffusion of plectonemes and a torque that rises after plectoneme formation with increasing linking number. The discovery of this new phase at the same time resolves the discrepancies between existing models and experiment.

cond-mat.soft

Multi-plectoneme phase of double-stranded DNA under torsion

We use the worm-like chain model to study supercoiling of DNA under tension and torque. The model reproduces experimental data for a much broader range of forces, salt concentrations and contour lengths than previous approaches. Our theory shows, for the first time, how the behavior of the system is controlled by a multi-plectoneme phase in a wide range of parameters. This phase does not only affect turn-extension curves but also leads to a non-constant torque in the plectonemic phase. Shortcomings from previous models and inconsistencies between experimental data are resolved in our theory without the need of adjustable parameters.

q-bio.BM

Stochastic model for nucleosome sliding in the presence of DNA ligands

Heat-induced mobility of nucleosomes along DNA is an experimentally well-studied phenomenon. A recent experiment shows that the repositioning is modified in the presence of minor-groove binding DNA ligands. We present here a stochastic three-state model for the diffusion of a nucleosome along DNA in the presence of such ligands. It allows us to describe the dynamics and the steady state of such a motion analytically. The analytical results are in excellent agreement with numerical simulations of this stochastic process.With this model, we study the response of a nucleosome to an external force and how it is affected by the presence of ligands.

cond-mat.soft

Kinetic proofreading of gene activation by chromatin remodeling

Gene activation in eukaryotes involves the concerted action of histone tail modifiers, chromatin remodellers and transcription factors, whose precise coordination is currently unknown. We demonstrate that the experimentally observed interactions of the molecules are in accord with a kinetic proofreading scheme. Our finding could provide a basis for the development of quantitative models for gene regulation in eukaryotes based on the combinatorical interactions of chromatin modifiers.

q-bio.MN

Nucleosome shape dictates chromatin-fiber structure

Apart from being the gateway for all access to the eukaryotic genome, chromatin has in recent years been identified as carrying an epigenetic code regulating transcriptional activity. The detailed knowledge of this code contrasts the ignorance of the fiber structure which it regulates, and none of the suggested fiber models are capable of predicting the most basic quantities of the fiber (diameter, nucleosome line density, etc.). We address this three-decade-old problem by constructing a simple geometrical model based on the nucleosome shape alone. Without fit parameters we predict the observed properties of the condensed chromatin fiber (e.g. its 30 nm diameter), the structure, and how the fiber changes with varying nucleosome repeat length. Our approach further puts the plethora of previously suggested models within a coherent framework, and opens the door to detailed studies of the interplay between chromatin structure and function.

q-bio.OT

Semi-classical buckling of stiff polymers

A quantitative theory of the buckling of a worm like chain based on a semi-classical approximation of the partition function is presented. The contribution of thermal fluctuations to the force-extension relation that allows to go beyond the classical Euler buckling is derived in the linear and non-linear regime as well. It is shown that the thermal fluctuations in the nonlinear buckling regime increase the end-to-end distance of the semiflexible rod if it is confined to 2 dimensions as opposed to the 3 dimensional case. Our approach allows a complete physical understanding of buckling in D=2 and in D=3 below and above the Euler transition.

cond-mat.soft

Controlled DNA compaction within chromatin: the tail-bridging effect

We study the mechanism underlying the attraction between nucleosomes, the fundamental packaging units of DNA inside the chromatin complex. We introduce a simple model of the nucleosome, the eight-tail colloid, consisting of a charged sphere with eight oppositely charged, flexible, grafted chains that represent the terminal histone tails. We demonstrate that our complexes are attracted via the formation of chain bridges and that this attraction can be tuned by changing the fraction of charged monomers on the tails. This suggests a physical mechanism of chromatin compaction where the degree of DNA condensation can be controlled via biochemical means, namely the acetylation and deacetylation of lysines in the histone tails.

q-bio.BM

Twirling DNA Rings - Swimming Nanomotors Ready for a Kickstart

We propose a rotary DNA nanomachine that shows a continuous rotation with a frequency of 10^2 -10^4 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 microns per second.

cond-mat.soft

Nucleosome interactions in chromatin: fiber stiffening and hairpin formation

We use Monte Carlo simulations to study attractive and excluded volume interactions between nucleosome core particles in 30 nm-chromatin fibers. The nucleosomes are treated as disk-like objects having an excluded volume and short range attraction modelled by a variant of the Gay-Berne potential. The nucleosomes are connected via bendable and twistable linker DNA in the crossed linker fashion. We investigate the influence of the nucleosomal excluded volume on the stiffness of the fiber. For parameter values that correspond to chicken erythrocyte chromatin we find that the persistence length is governed to a large extent by that excluded volume whereas the soft linker backbone elasticity plays only a minor role. We further find that internucleosomal attraction can induce the formation of hairpin configurations. Tension-induced opening of such configurations into straight fibers manifests itself in a quasi-plateau in the force-extension curve that resembles results from recent micromanipulation experiments. Such hairpins may play a role in the formation of higher order structures in chromosomes like chromonema fibers.

q-bio.SC

The physics of chromatin

Recent progress has been made in the understanding of the physical properties of chromatin -- the dense complex of DNA and histone proteins that occupies the nuclei of plant and animal cells. Here I will focus on the two lowest levels of the hierarchy of DNA folding into the chromatin complex: (i) the nucleosome, the chromatin repeating unit consisting of a globular aggregate of eight histone proteins with the DNA wrapped around: its overcharging, the DNA unwrapping transition, the ''sliding'' of the octamer along the DNA. (ii) The 30nm chromatin fiber, the necklace-like structure of nucleosomes connected via linker DNA: its geometry, its mechanical properties under stretching and its response to changing ionic conditions. I will stress that chromatin combines two seemingly contradictory features: (1) high compaction of DNA within the nuclear envelope and at the same time (2) accessibility to genes, promoter regions and gene regulatory sequences.

cond-mat.soft

Charged rosettes at high and low ionic strengths

The complexation between a semiflexible polyelectrolyte and an oppositely charged macroion leads to a multitude of structures ranging from tight complexes with the chain wrapped around the macroion to open multileafed rosette-like complexes. Rosette structures, expected to occur for short-ranged attractions between the macroion and the chain, have now also been seen in recent Monte Carlo simulations with long-range (unscreened) interactions [Akinchina and Linse Macromolecules 2002, 35, 5183]. The current study provides scaling theories for both cases and shows that rosette structures are indeed quite robust against changes in the ionic strength. However, the transition from the wrapped to the rosette configuration has a dramatically different characteristics: The short-range case leads to a strongly discontinuous transition into a rosette with large leaves whereas the long-range case occurs in a continuous fashion. We provide the complete diagram of states for both cases.

cond-mat.soft

How short-ranged electrostatics controls the chromatin structure on much larger scales

We propose that the degree of sweeling of the 30nm chromatin fiber (a "measure" of its transcriptional activity) is mainly determined by the short-ranged electrostatical interaction between different sections of the "folded" DNA chain. These sections constitute only a small fraction of the chain and they are located close to the entry-exit points of the DNA chain at the nucleosome core particles. We present a model that allows to estimate the degree of swelling of chromatin fibers as a function of salt concentration, charge density of the strands etc. Different mechanisms by which the state of chromatin can be controlled in vitro and in vivo are discussed.

cond-mat.soft