Biology subjects

Schiessel, H.

Publications and source records attributed to Schiessel, H..

8 recordsLinked to original sources

bioRxiv2026

Repulsion-Driven Layering in Polymer-Assisted Condensation

The hierarchical organization of multiphase biomolecular condensates into core-shell architectures is a fundamental problem in soft matter and biophysics. While classical explanations rely on hierarchies of interfacial tension ({gamma}) between coexisting liquids, the ultralow tensions of condensates (0.1-1 {micro}N/m) render such hierarchies potentially fragile. We introduce a robust assembly principle based on Polymer-Assisted Condensation (PAC), in which a single polymer species dictates the entire structure. The polymer nucleates a dense core by recruiting a condensation-incompetent protein (P1). A second incompetent protein (P2), which is repelled or otherwise thermodynamically disfavored from entering the polymer-rich core, is nonetheless recruited to the interface by weak attraction to P1, forming a stable shell. This effective repulsion-driven layering operates across a wide parameter space without requiring{gamma} asymmetries and yields a robust structure that is impervious to concentration fluctuations and environmental perturbations. Phase-field modeling and molecular simulations establish this mechanism and capture key features of nucleolar organization. Our work reveals a general physical pathway for encoding spatial order in soft, multicomponent fluids.

biophysics↗

bioRxiv2025

MDNA: a software module for DNA structure generation and analysis

Exploring the dynamical and structural properties of molecular complexes involving DNA is a fundamentally important aspect of understanding many biological processes. Although tools exist for modeling linear DNA and simple complexes, significant challenges remain in generating intricate biomolecular assemblies and incorporating biologically relevant modifications. These limitations restrict the ability to create accurate starting configurations for advanced molecular simulation studies. Here, we introduce MDNA, a molecular modeling toolkit that bridges these gaps by enabling the construction and analysis of complex DNA structures. MDNA offers a versatile solution to generate DNA shapes using a spline-based mapping technique that enables the construction of DNA configurations with arbitrary shapes. Key features include support for (non-)canonical base modifications, such as Watson-Crick-Franklin to Hoogsteen transitions, DNA methylation, and the ability to refine structures using Monte Carlo minimization. The toolkit also provides geometric analysis tools based on rigid body formalism to evaluate DNA structures and trajectories. Together, these features enable users to model and analyze DNA configurations in high detail with a modular Python interface. By integrating structure generation and analysis into a single workflow, MDNA improves the study of DNA-protein interactions, paving the way for new insights into DNA dynamics and molecular simulations.

biophysics↗

bioRxiv2025

The Effects of DMSO on DNA Conformations and Mechanics

Dimethyl sulfoxide (DMSO) is a polar aprotic solvent used in a wide range of applications, including uses as a drug and in drug delivery, as a solvent for fluorescence dyes, and in enzymatic reactions that process DNA. Consequently, many assays contain low concentrations ([≤] 10%) of DMSO. While it is well known that DMSO lowers the melting temperature of DNA, its effects on DNA conformations and mechanical properties below the melting temperature are unclear. Here we use complementary single-molecule techniques to probe DNA in the presence of 0-60% DMSO. Magnetic tweezers force-extension measurements find that the bending persistence length of DNA decreases moderately and linearly with DMSO concentrations up to 20 vol%, by (0.43 {+/-} 0.02)% per %-DMSO, respectively. Magnetic tweezers twist measurements demonstrate a reduction in melting torque in the presence of DMSO and find that the helical twist of DNA remains largely unchanged up to 20% DMSO, while even higher concentrations slightly unwind the helix. Using AFM imaging, we find a moderate compaction of DNA conformations by DMSO and observe a systematic decrease of the mean squared end-to-end distance by 1.2% per %-DMSO. We use coarse grained Monte Carlo simulations of DNA as a semi-flexible polymer with a variable density of flexible segments or bubbles, representing DMSO-induced local defects or melting, to rationalize the observed behavior. The model quantitates the effects of introducing locally flexible regions into DNA and gives trends in line with the magnetic tweezers and AFM imaging experiments. Our results show that addition of up to 50% DMSO has a gradual effect on DNA structure and mechanics and that for low concentrations ([≤] 20%) the induced changes are relatively minor. Our work provides a baseline to understand and model the effects of DMSO on DNA in a range of biophysical and biochemical assays. STATEMENT OF SIGNIFICANCEDimethyl sulfoxide (DMSO) is a widely used polar aprotic solvent. It is employed e.g. as a drug and in drug delivery, as a solvent for small molecules, and as an additive to enzymatic reactions that process DNA. Despite its wide-spread use, its effects on DNA conformations and properties are not well understood and often neglected. We use single-molecule manipulation with magnetic tweezers and AFM imaging to probe DNA in the presence of 0-60% DMSO. We find that DMSO increases the flexibility of DNA, leading to more compact conformations. Up to 50% DMSO, the induced changes are gradual and approximately linear. Our results provide a quantitative baseline to understand, model, and optimize assays with DNA in the presence of DMSO.

biophysics↗

bioRxiv2022

Loop extrusion driven volume phase transition of entangled chromosomes

Mitotic chromosomes without nucleosomes have been reconstituted in recent experiments. When topo II is depleted from the reconstituted chromosomes, these chromosomes are entangled and form sparklers, where DNA is condensed in the core with linker histone H1.8 and condensin is localized at the periphery. To understand the mechanism of the assembly of sparklers, we here take into account the loop extrusion by condensin in an extension of the theory of entangled polymer gels. The loop extrusion stiffens an entangled DNA network because DNA segments in the elastically effective chains are translocated to loops, which are elastically ineffective. Our theory predicts that the loop extrusion by condensin drives the volume phase transition that collapses a swollen entangled DNA gel as the stiffening of the network destabilizes the swollen phase. This is an important element to understand the mechanism of the assembly of the reconstituted chromosomes.

biophysics↗

bioRxiv2021

Polymer-Assisted Condensation: A Mechanism for Hetero-Chromatin Formation and Epigenetic Memory

We consider the formation of droplets from a 2-component liquid mixture induced by a large polymer chain that has preferential solubility with one of the components. We assume that the liquid mixture is in a fully miscible state, but far above the critical interaction limit of the two species. We show that the polymer coil acts as a chemical potential trap, which can shift the mixture inside the polymer volume into the partially miscible state and thus triggers the formation of a polymer-bound droplet of the preferred solvent phase which we denote as polymer-assisted condensation (PAC). We propose a simple mean-field model which can predict the essential feature of PAC and perform molecular-dynamics simulations to show that the predicted phase behavior is robust against fluctuation effects. Our model aims to understand the formation of macromolecular condensates inside the cell nucleus, such as those formed by heterochromatin 1 (HP1). We propose that such droplets organize the spatial structure of chromatin into hetero- and euchromatin and ensure the propagation of epigenetic information through the cell generations.

biophysics↗

bioRxiv2021

Slow chromatin dynamics enhances promoter accessibility to transcriptional condensates

Enhancers are DNA sequences at a long genomic distance from target genes. Recent experiments suggest that enhancers are anchored to the surfaces of condensates of transcription machinery and that the loop extrusion process enhances the transcription level of their target genes. Here we theoretically study the polymer dynamics driven by the loop extrusion of the linker DNA between an enhancer and the promoter of its target gene to calculate the contact probability of the promoter to the transcription machinery in the condensate. Our theory predicts that when the loop extrusion process is active, the contact probability increases with increasing linker DNA length. This finding reflects the fact that the relaxation time, with which the promoter stays in proximity to the surface of the transcriptional condensate, increases as the length of the linker DNA increases. This contrasts the equilibrium case for which the contact probability between the promoter and the transcription machineries is smaller for longer linker DNA lengths.

biophysics↗

bioRxiv2020

Phase separation of chromatin brush driven by enzymatic reaction dynamics of histone posttranslational modifications

The nuclei of undifferentiated cells show uniform decompacted chromatin while during development nuclei decrease in size and foci of condensed chromatin appear, reminiscent of phase separation. This study is motivated by recent experiments that suggest that the unbinding of enzymes that chemically modify (acetylate) histone tails causes decompaction of condensed chromatin. Here we take into account the enzymatic reactions of histone modifications to predict the phase separation of chromatin in a model system, the chromatin brush, which mimics chromatin at the proximity of a nuclear membrane. The model contains activators and silencers, which change the state of the nucleosomes to (transcriptionally) active or inactive via the Michaelis-Menten kinetics. Our theory predicts that the chromatin brush will phase separate when the brush height is reduced below a threshold height. The phase separation is driven by an anti-correlation: Activators change the state of nucleosomes to the active state suppressing the binding of silencers to these nucleosomes and vice versa.

biophysics↗

bioRxiv2020

Pioneer transcription factors in chromatin remodeling: the kinetic proofreading view

Pioneer transcription factors are a recently defined class of transcription factors which can bind directly to nucleosomal DNA; they play a key role in gene activation in certain pathways. Here we quantify their role in the initiation of nucleosome displacement within the kinetic proofreading scenario of chromatin remodeling. The model allows to perform remodeling efficiency comparisons for scenarios involving different types of transcription factors and remodelers as a function of their binding and unbinding rates and concentrations. Our results demonstrate a novel way to fine-tune the specificity of processes that modify the chromatin structure in transcriptional initiation.

biophysics↗