Modelling the effect of ribosome mobility on the rate of protein synthesis

Translation is one of the main steps in the synthesis of proteins. It consists of ribosomes that translate sequences of nucleotides encoded on mRNA into polypeptide sequences of amino acids. Ribosomes bound to mRNA move unidirectionally, while unbound ribosomes diffuse in the cytoplasm. It has been hypothesized that finite diffusion of ribosomes plays an important role in ribosome recycling and that mRNA circularization enhances the efficiency of translation. In order to estimate the effect of cytoplasmic diffusion on the rate of translation, we consider a Totally Asymmetric Simple Exclusion Process (TASEP) coupled to a finite diffusive reservoir, which we call the Ribosome Transport model with Diffusion (RTD). In this model, we derive an analytical expression for the rate of protein synthesis as a function of the diffusion constant of ribosomes, which is corroborated with results from continuous-time Monte Carlo simulations. Using a wide range of biological relevant parameters, we conclude that diffusion in biological cells is fast enough so that it does not play a role in controlling the rate of translation initiation.Comment: article, 16 pages, 5 figure

Modeling supercoiled DNA interacting with an anchored cluster of proteins: towards a quantitative estimation of chromosomal DNA supercoiling

We investigate the measurement of DNA supercoiling density ($\sigma$) along chromosomes using interaction frequencies between DNA and DNA-anchored clusters of proteins. Specifically, we show how the physics of DNA supercoiling leads, in bacteria, to the quantitative modeling of binding properties of ParB proteins around their centromere-like site, {\it parS}. Using this framework, we provide an upper bound for $\sigma$ in the {\it Escherichia coli} chromosome, consistent with plasmid values, and offer a proof of concept for a high accuracy measurement. To reach these conclusions, we revisit the problem of the formation of ParB clusters. We predict, in particular, that they result from a non-equilibrium, stationary balance between an influx of produced proteins and an outflux of excess proteins, i.e., they behave like liquid-like protein condensates with unconventional ``leaky'' boundaries.Comment: 5 pages + Supplementary Info (including 3 figures

Signature of (anti)cooperativity in the stochastic fluctuations of small systems: application to the bacterial flagellar motor

The cooperative binding of molecular agents onto a substrate is pervasive in living systems. To study whether a system shows cooperativity, one can rely on a fluctuation analysis of quantities such as the number of substrate-bound units and the residence time in an occupancy state. Since the relative standard deviation from the statistical mean monotonically decreases with the number of binding sites, these techniques are only suitable for small enough systems, such as those implicated in stochastic processes inside cells. Here, we present a general-purpose grand canonical Hamiltonian description of a small one-dimensional (1D) lattice gas with either nearest-neighbor or long-range interactions as prototypical examples of cooperativity-influenced adsorption processes. First, we elucidate how the strength and sign of the interaction potential between neighboring bound particles on the lattice determine the intensity of the fluctuations of the mean occupancy. We then employ this relationship to compare the theoretical predictions of our model to data from single molecule experiments on bacterial flagellar motors (BFM) of E. coli. In this way, we find evidence that cooperativity controls the mechano-sensitive dynamical assembly of the torque-generating units, the so-called stator units, onto the BFM. Furthermore, in an attempt to quantify fluctuations and the adaptability of the BFM, we estimate the stator-stator interaction potential. Finally, we conclude that the system resides in a sweet spot of the parameter space (phase diagram) suitable for a smoothly adaptive system while minimizing fluctuations.Comment: 35 pages, 18 figures, 4 table

Erratum to: Modelling the effect of ribosome mobility on the rate of protein synthesis

A Correction to this paper has been published: 10.1140/epje/s10189-021-00019-

Supercoiled DNA and non-equilibrium formation of protein complexes: A quantitative model of the nucleoprotein ParBS partition complex

International audienceParAB S , the most widespread bacterial DNA segregation system, is composed of a centromeric sequence, parS , and two proteins, the ParA ATPase and the ParB DNA binding proteins. Hundreds of ParB proteins assemble dynamically to form nucleoprotein parS -anchored complexes that serve as substrates for ParA molecules to catalyze positioning and segregation events. The exact nature of this ParB S complex has remained elusive, what we address here by revisiting the Stochastic Binding model (SBM) introduced to explain the non-specific binding profile of ParB in the vicinity of parS . In the SBM, DNA loops stochastically bring loci inside a sharp cluster of ParB. However, previous SBM versions did not include the negative supercoiling of bacterial DNA, leading to use unphysically small DNA persistences to explain the ParB binding profiles. In addition, recent super-resolution microscopy experiments have revealed a ParB cluster that is significantly smaller than previous estimations and suggest that it results from a liquid-liquid like phase separation. Here, by simulating the folding of long (≥ 30 kb) supercoiled DNA molecules calibrated with realistic DNA parameters and by considering different possibilities for the physics of the ParB cluster assembly, we show that the SBM can quantitatively explain the ChIP-seq ParB binding profiles without any fitting parameter, aside from the supercoiling density of DNA, which, remarkably, is in accord with independent measurements. We also predict that ParB assembly results from a non-equilibrium, stationary balance between an influx of produced proteins and an outflux of excess proteins, i.e., ParB clusters behave like liquid-like protein condensates with unconventional “leaky” boundaries

Surfing on protein waves: proteophoresis as a mechanism for bacterial genome partitioning

6 pages, 3 figuresInternational audienceEfficient bacterial chromosome segregation typically requires the coordinated action of a three-component machinery, fueled by adenosine triphosphate, called the partition complex. We present a phenomenological model accounting for the dynamic activity of this system that is also relevant for the physics of catalytic particles in active environments. The model is obtained by coupling simple linear reaction-diffusion equations with a proteophoresis, or “volumetric” chemophoresis, force field that arises from protein-protein interactions and provides a physically viable mechanism for complex translocation. This minimal description captures most known experimental observations: dynamic oscillations of complex components, complex separation, and subsequent symmetrical positioning. The predictions of our model are in phenomenological agreement with and provide substantial insight into recent experiments. From a nonlinear physics view point, this system explores the active separation of matter at micrometric scales with a dynamical instability between static positioning and traveling wave regimes triggered by the dynamical spontaneous breaking of rotational symmetry

A conserved mechanism drives partition complex assembly on bacterial chromosomes and plasmids

Synopsis Chromosome and plasmid segregation in bacteria are mostly driven by ParABS systems. These DNA partitioning machineries rely on large nucleoprotein complexes assembled on centromere sites (parS). However, the mechanism of how a few parS-bound ParB proteins nucleate the formation of highly concentrated ParB clusters remains unclear despite several proposed physico-mathematical models. We discriminated between these different models by varying some key parameters in vivo using the F plasmid partition system. We found that "Nucleation & caging" is the only coherent model recapitulating in vivo data. We also showed that the stochastic self-assembly of partition complexes (i) is a robust mechanism, (ii) does not directly involve ParA ATPase, (iii) results in a dynamic structure of discrete size independent of ParB concentration, and (iv) is not perturbed by active transcription but is by protein complexes. We refined the "Nucleation & caging" model and successfully applied it to the chromosomally encoded Par system of Vibrio cholerae, indicating that this stochastic self-assembly mechanism is widely conserved from plasmids to chromosomes

Poétisation de l'histoire et de la politique

Ce numéro sur « Poétisation de l’histoire et de la politique » s’inscrit dans le cadre de l’axe culturel, portant sur les représentations sociales et textuelles de réalités historiques et politiques, de l’équipe du MIMMOC (EA 3812). Ses éditeurs se penchent sur l’interaction entre des champs disciplinaires différents : l’histoire (ses traces, sa perception, son écriture, ses représentations) et son esthétisation, qu’ils ont qualifiée de poétisation, du point de vue rhétorique, graphique ou iconographique, qu’il s’agisse de peinture, de cinéma ou de toute autre représentation par l’image. S’appuyant d’une part sur le concept désormais bien établi du « lieu de mémoire » dans ses deux acceptions, matérielle et immatérielle, développées par Pierre Nora et ses successeurs, mais aussi sur le concept de « poésie » et d’ « aura » défini par Walter Benjamin à propos de l’œuvre d’art, puis revisité par les travaux de Paul Ricoeur et de Roland Barthes sur l’icône et l’image (notamment la photographie), un groupe de chercheurs issus de plusieurs champs disciplinaires (études anglo-américaines, germaniques, hispaniques, italiennes, lusophones, néo-helléniques, slaves, mais aussi histoire contemporaine, lettres modernes ou littérature comparée), s’est réuni pour analyser le lien entre l’événement et son esthétisation et les correspondances entre les divers domaines impliqués. Le numéro comporte quatre chapitres : le premier, « Histoire et écriture » questionne l’écriture de l’histoire pour voir comment le réel est retranscrit ou interprété (3 articles, de Jérôme Grévy, Michel Riaudel et Sanja Boskovic). Le deuxième, « La poésie des lieux » (2 articles), porte sur la poésie qui émane des vestiges (Geneviève Puig, Isabelle Solères). Le troisième, « Poétisation artistique et littéraire » (5 articles), s’intéresse aux représentations littéraires (Geoffrey Pitcher, Marie-Catherine Chanfreau, Elvire Diaz, Alix Mary-Tubman, Sandra Teixeira). Le dernier, « Poétisation en images et en twitt » (3 articles), porte sur le cinéma et sur twitter (Jeremy Price, Pascal Vacher, Noémie Suisse). This issue on "Poetising history and politics" follows the cultural studies research on social and textual representation of historical and political reality conducted within the MIMMOC research group (EA 3812). The editors have concentrated on the interaction between varied disciplinary fields : history (traces, perception, writing, representation) and its aesthetic value, which they have chosen to term 'poetising', in a rhetorical, graphic or iconographic from, whether painting, cinema or any other image form. Using on the one hand the well-established concept of "places of memory" in its two senses, both material and immaterial, developed by Pierre Nora and his followers, and on the other hand on the concept of "poetry" and "aura" defined by Walter Benjamin in respect of works of art, then reutilised in the works of Paul Ricoeur and Roland Barthes on the icone and images (in particular photography, a group of academics from several disciplinary fields (area studies - English, German, Spanish, Italian, Portuguese, Greek, Slavic - contemporary history, French literature, comparative literature), analyse both the link between an event and its aethestic translation and the interactions between the different fields involved. The issue is divided into four sections : the first, "History and writing" asks how the (re-)writing of history restranscribes or reinterprets reality (3 articles by Jérôme Grévy, Michel Riaudel et Sanja Boskovic). The second, "The poetry of place" (2 articles), looks at the poetry that emanates from ruins (Geneviève Puig, Isabelle Solères). The third part, "Artistic and literary poetising" (5 articles), looks at litterary representations (Geoffrey Pitcher, Marie-Catherine Chanfreau, Elvire Diaz, Alix Mary-Tubman, Sandra Teixeira). The final section, "Poetising in pictures and by tweet" (3 articles), concerns the film and twitter media (Jeremy Price, Pascal Vacher, Noémie Suisse)