Biology subjects

Scolari, V. F.

Publications and source records attributed to Scolari, V. F..

4 recordsLinked to original sources

bioRxiv2025

Compaction and swelling of single stretched DNAs driven by molecular crowding

We present a theory for the effects of osmotic pressure exerted by macromolecular crowders, on a double-stranded DNA or other semiflexible polymer extended by tension. Our results predict the force and crowder-density dependence of the polymer extension. The lowest-order effect is a crowder-dependent compression that counteracts the external stretching force, which can collapse the polymer at a crowder-dependent critical force f*. This compression is dependent on crowder radius r and density{phi} , with higher densities and smaller radii having greater effects on the force-extension curve. At first order in perturbation theory we also find a fluctuation-dependent correction to the depletion volume, which can overwhelm the simple compression effect for large crowders, leading to expansion of the polymer.

biophysics↗

bioRxiv2023

Empirical modeling of a single polymer collapsing under the entropic pressure of neutral crowders

Macromolecular crowding can induce the collapse of a single long polymer into a globular form due to depletion forces of entropic nature. This phenomenon has been shown to play a significant role in compacting the genome within the bacterium Escherichia coli into a well-defined region of the cell known as the nucleoid. Motivated by the biological significance of this process, numerous theoretical and computational studies have searched for the primary determinants of the behavior of polymer-crowder phases. However, our understanding of this process remains incomplete and there is debate on a quantitatively unified description. In particular, different simulation studies with explicit crowders have proposed different order parameters as potential predictors for the collapse transition. In this work, we present a comprehensive analysis of published simulation data obtained from different sources. Based on the common behavior we find in this data, we develop a unified phenomenological model that we show to be predictive. Finally, to further validate the accuracy of the model, we conduct new simulations on polymers of various sizes, and investigate the role of jamming of the crowders.

biophysics↗

bioRxiv2021

Live-cell micromanipulation of a genomic locus reveals interphase chromatin mechanics

Our understanding of the physical principles organizing the genome in the nucleus is limited by the lack of tools to directly exert and measure forces on interphase chromosomes in vivo and probe their material nature. Here, we present a novel approach to actively manipulate a genomic locus using controlled magnetic forces inside the nucleus of a living human cell. We observe viscoelastic displacements over microns within minutes in response to near-picoNewton forces, which are well captured by a Rouse polymer model. Our results highlight the fluidity of chromatin, with a moderate contribution of the surrounding material, revealing the minor role of crosslinks and topological effects and challenging the view that interphase chromatin is a gel-like material. Our new technology opens avenues for future research, from chromosome mechanics to genome functions.

biophysics↗

bioRxiv2020

The silencing factor Sir3 is a molecular bridge that sticks together distant loci

Physical contacts between distant loci contribute to regulate genome function. However, the molecular mechanisms responsible for settling and maintaining such interactions remain poorly understood. Here we investigate the well conserved interactions between heterochromatin loci. In budding yeast, the 32 telomeres cluster in 3-5 foci in exponentially growing cells. This clustering is functionally linked to the formation of heterochromatin in subtelomeric regions through the recruitment of the silencing complex SIR composed of Sir2/3/4. Combining microscopy and Hi-C on strains expressing different alleles of SIR3, we show that the binding of Sir3 directly promotes long range contacts between distant regions, including the rDNA, telomeres, and internal Sir3 bound sites. Furthermore, we unveil a new property of Sir3 in promoting rDNA compaction. Finally, using a synthetic approach we demonstrate that Sir3 can bond loci belonging to different chromosomes together, when targeted to these loci, independently of its interaction with its known partners (Rap1, and Sir4), Sir2 activity or chromosome context. Altogether these data suggest that Sir3 represents an uncommon example of protein able to bridge directly distant loci.

cell biology↗