Biology subjects

Zaburdaev, V.

Publications and source records attributed to Zaburdaev, V..

24 records · Page 2Linked to original sources

bioRxiv2020

Thermal fluctuations assist mechanical signal propagation in coiled-coil proteins

Recently it has been shown that the long coiled-coil membrane tether protein Early Endosome Antigen 1 (EEA1) switches from a rigid to a flexible conformation upon binding of a signaling protein to its free end. This flexibility switch represents a novel motor-like activity, allowing EEA1 to generate a force that moves vesicles closer to the membrane they will fuse with. To elucidate how binding of a single signaling protein can globally change the stiffness of a 200 nm long chain, we propose a simplified description of the coiled-coil as a one-dimensional Frenkel-Kontorova chain. Using numerical simulations, we find that an initial perturbation of the chain can propagate along its whole length in the presence of thermal fluctuations, changing the configuration of the entire molecule and thereby affecting its stiffness. Our work sheds light onto intramolecular communication and force generation in long coiled-coil proteins.

biophysics↗

bioRxiv2020

Continuum theory of active phase separation in cellular aggregates

Dense cellular aggregates are common in many biological settings, ranging from bacterial biofilms to organoids, cell spheroids and tumors. Motivated by Neisseria gonorrhoeae biofilms as a model system, we present a hydrodynamic theory to study dense, active, viscoelastic cellular aggregates. The dynamics of these aggregates, driven by forces generated by individual cells, is intrinsically out-of-equilibrium. Starting from the force balance at the level of individual cells, we arrive at the dynamic equations for the macroscopic cell number density via a systematic coarse-graining procedure taking into account a nematic tensor of intracellular force dipoles. We describe the basic process of aggregate formation as an active phase separation phenomenon. Our theory furthermore captures how two cellular aggregates coalesce. Merging of aggregates is a complex process exhibiting several time scales and heterogeneous cell behaviors as observed in experiments. In our theory, it emerges as a coalescence of active viscoelastic droplets where the key timescales are linked to the turnover of the active force generation. Our theory provides a general framework to study the rheology and dynamics of dense cellular aggregates out of thermal equilibrium.

biophysics↗

bioRxiv2019

Quantitative measurements of chromatin modification dynamics during zygotic genome activation

Histone posttranslational modifications (PTMs) are key gene expression regulators, but their rapid dynamics during development remain difficult to capture. We describe an approach that images fluorescent antibody fragments to quantify PTM enrichment and active transcription at defined loci during zygotic genome activation in living zebrafish embryos. The technique reveals a drastic increase in histone H3 Lys27 acetylation (H3K27ac) before genome activation both at a specific locus and globally.

cell biology↗

bioRxiv2018

Intracellular mass density increase is accompanying but not sufficient for stiffening and growth arrest of yeast cells

Many organisms, including yeast cells, bacteria, nematodes and tardigrades, endure harsh environmental conditions, such as nutrient scarcity, or lack of water and energy for a remarkably long time. The rescue programs that these organisms launch upon encountering these adverse conditions include reprogramming their metabolism in order to enter a quiescent or dormant state in a controlled fashion. Reprogramming coincides with changes in the macromolecular architecture and changes in the physical and mechanical properties of the cells. However, the cellular mechanisms underlying the physical-mechanical changes remain enigmatic. Here, we induce metabolic arrest of yeast cells by lowering their intracellular pH. We then determine the differences in the intracellular mass density and stiffness of active and metabolically arrested cells using optical diffraction tomography and atomic force microscopy. We show that an increased intracellular mass density is associated with an increase in stiffness when the growth of yeast is arrested. However, increasing the intracellular mass density alone is not sufficient for maintenance of the growth-arrested state in yeast cells. Our data suggest that the cytoplasm of metabolically arrested yeast displays characteristics of solid. Our findings constitute a bridge between the mechanical behavior of the cytoplasm and the physical and chemical mechanisms of metabolically arrested cells with the ultimate aim of understanding dormant organisms.

biophysics↗

bioRxiv2017

Transcription establishes microenvironments that organize euchromatin

Chromatin is organized into heterochromatin, which is transcriptionally inactive, and euchromatin, which can switch between transcriptionally active and inactive states. This switch in euchromatin activity is accompanied by changes in its spatial distribution. How euchromatin rearrangements are established is unknown. Here we use super-resolution and live-cell microscopy to show that transcriptionally inactive euchromatin moves away from transcriptionally active euchromatin. This movement is driven by the formation of RNA-enriched microenvironments that exclude inactive euchromatin. Using theory, we show that the segregation into RNA-enriched microenvironments and euchromatin domains can be considered an active microemulsion. The tethering of transcripts to chromatin via RNA polymerase II forms effective amphiphiles that intersperse the two segregated phases. Taken together with previous experiments, our data suggest that chromatin is organized in the following way: heterochromatin segregates from euchromatin by phase separation, while transcription organizes euchromatin similar to an active microemulsion.

cell biology↗

bioRxiv2017

Competition between histone and transcription factor binding regulates the onset of transcription in zebrafish embryos

SUMMARYUpon fertilization, the genome of animal embryos remains transcriptionally inactive until the maternal-to-zygotic transition. At this time, the embryo takes control of its development and transcription begins. How the onset of zygotic transcription is regulated remains unclear. Here, we show that a dynamic competition for DNA binding between nucleosome-forming histones and transcription factors regulates zebrafish genome activation. Taking a quantitative approach, we found that the concentration of non-DNA bound core histones sets the time for the onset of transcription. The reduction in nuclear histone concentration that coincides with genome activation does not affect nucleosome density on DNA, but allows transcription factors to compete successfully for DNA binding. In agreement with this, transcription factor binding is sensitive to histone levels and the concentration of transcription factors also affects the time of transcription. Our results demonstrate that the relative levels of histones and transcription factors regulate the onset of transcription in the embryo.

developmental biology↗