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Production scientifique
Physique théorique des systèmes biologiques
(9) Production(s) de l'année 2021
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Genomic physics: biophysical modeling confronted to genomic data
Auteur(s): Walter J.-C.
Conférence invité: Labex NUMEV Days (Montpellier, FR, 2021-11)
Texte intégral en Openaccess :
Ref HAL: hal-03428118_v1
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Résumé: The last decade has seen a spectacular development of genomic physics both in bacteria and eukaryotes. This is due in large part to the development of experimental techniques, which allow to probe (i) the motion of nucleic acids (chromosomal DNA and RNA) in vivo by means of microscopy techniques and (ii) the interactions of these nucleic acids with other actors of the cell (like proteins and molecular motors) by means of high-throughput sequencing techniques. I will focus on three different processes : (i) the modeling of translation with a ballistic model describing the motion of ribosomes on messenger RNA, (ii) the physical mechanism of liquid-liquid phase separation, which is found to be universally spread in the cells to increase, locally and transiently, the concentration of a molecular actor (proteins, RNA etc.). We illustrate this process with the example of the bacterial DNA segregation where liquid-liquid phase separation is used to increase the local concentration in order to catalyze ATP hydrolysis. Finally (iii) I give a general framework on how polymer physics can help to infer the organization of DNA in vivo from microscopy and high-throughput sequencing experiments and apply it to the modeling of bacterial DNA in Escherichia coli and to the epigenetic regulation via polycomb domains in Drosophila.
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Ionic Conductance of Carbon Nanotubes: Confronting Literature Data with Nanofluidic Theory
Auteur(s): Manghi Manoel, Palmeri J., Henn F., Noury A., Picaud Fabien, Herlem Guillaume, Jourdain V.
(Article) Publié:
The Journal Of Physical Chemistry C, vol. 125 p.22943-22950 (2021)
Texte intégral en Openaccess :
Ref HAL: hal-03360790_v1
DOI: 10.1021/acs.jpcc.1c08202
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Résumé: The field of ion transport through carbon nanotubes (CNTs) is marked by a large variability of the ionic conductance values reported by different groups. There is also a large uncertainty concerning the relative contributions of channel and access resistances in the experimentally measured currents, both depending on experimental parameters (nanotube length and diameter). In this perspective article, we discuss the ionic conductance values reported so far in the case of 2 individual CNTs and compare them with standard nano-fluidic models considering both the access and channel resistances. With a view toward guiding experimentalists, we thus show in which conditions the access or the channel resistance can predominate in CNTs. We explain in particular that it is not justified to use phenomenological models neglecting the channel resistance in the case of micrometer-long CNTs. This comparison reveals that most experimental conductance values can be explained in the framework of current nanofluidic models by considering experimental variations of slip length and surface charge density and that just a few extraordinarily high values cannot be accounted for even using extreme parameter values. Finally, we discuss how to complete existing models and how to improve the statistical reliability of experimental data in the field.
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Competition between Born solvation, dielectric exclusion, and Coulomb attraction in spherical nanopores
Auteur(s): Hennequin Théo, Manghi Manoel, Palmeri J.
(Article) Publié:
Physical Review E: Statistical, Nonlinear, And Soft Matter Physics, vol. 104 p.044601 (2021)
Texte intégral en Openaccess :
Ref HAL: hal-03350648_v1
Ref Arxiv: 2104.14824
DOI: 10.1103/PhysRevE.104.044601
Ref. & Cit.: NASA ADS
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Résumé: The recent measurement of a very low dielectric constant, $\epsilon$, of water confined in nanometric slit pores leads us to reconsider the physical basis of ion partitioning into nanopores. For confined ions in chemical equilibrium with a bulk of dielectric constant $\epsilon_b>\epsilon$, three physical mechanisms, at the origin of ion exclusion in nanopores, are expected to be modified due to this dielectric mismatch: dielectric exclusion at the water-pore interface (with membrane dielectric constant, $\epsilon_m<\epsilon$), the solvation energy related to the difference in Debye-H\"uckel screening parameters in the pore, $\kappa$, and in the bulk $\kappa_b$, and the classical Born solvation self-energy proportional to $\epsilon^{-1}-\epsilon_b^{-1}$. Our goal is to clarify the interplay between these three mechanisms and investigate the role played by the Born contribution in ionic liquid-vapor (LV) phase separation in confined geometries. We first compute analytically the potential of mean force (PMF) of an ion of radius $R_i$ located at the center of a nanometric spherical pore of radius $R$. Computing the variational grand potential for a solution of confined ions, we then deduce the partition coefficients of ions in the pore. Phase diagrams of the LV transition are established for various parameter values and we show that a signature of this phase transition can be detected by monitoring the total osmotic pressure. For charged nanopores, these exclusion effects compete with the electrostatic attraction that imposes the entry of counterions into the pore to enforce electro-neutrality. This study will therefore help in deciphering the respective roles of the Born self-energy and dielectric mismatch in experiments and simulations of ionic transport through nanopores.
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Modeling and live imaging of mechanical instabilities in the zebrafish aorta during hematopoiesis
Auteur(s): Chalin Dmitrii, Bureau Charlotte, Parmeggiani A., Rochal Sergei, Kissa Karima, Golushko I.
(Article) Publié:
Scientific Reports, vol. 11 p.9316 (2021)
Texte intégral en Openaccess :
Ref HAL: hal-03323839_v1
PMID 33927284
DOI: 10.1038/s41598-021-88667-w
WoS: WOS:000656206800045
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Résumé: All blood cells originate from hematopoietic stem/progenitor cells (HSPCs). HSPCs are formed from endothelial cells (ECs) of the dorsal aorta (DA), via endothelial-to-hematopoietic transition (EHT). The zebrafish is a primary model organism to study the process in vivo. While the role of mechanical stress in controlling gene expression promoting cell differentiation is actively investigated, mechanisms driving shape changes of the DA and individual ECs remain poorly understood. We address this problem by developing a new DA micromechanical model and applying it to experimental data on zebrafish morphogenesis. The model considers the DA as an isotropic tubular membrane subjected to hydrostatic blood pressure and axial stress. The DA evolution is described as a movement in the dimensionless controlling parameters space: normalized hydrostatic pressure and axial stress. We argue that HSPC production is accompanied by two mechanical instabilities arising in the system due to the plane stress in the DA walls and show how a complex interplay between mechanical forces in the system drives the emerging morphological changes.
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Macrophage morphological plasticity and migration is Rac signalling and MMP9 dependant
Auteur(s): Travnickova Jana, Nhim Sandra, Abdellaoui Naoill, Djouad Farida, Nguyen-Chi Mai, Parmeggiani A., Kissa Karima
(Article) Publié:
Scientific Reports, vol. 11 p.10123 (2021)
Texte intégral en Openaccess :
Ref HAL: hal-03323838_v1
PMID 33980872
DOI: 10.1038/s41598-021-88961-7
WoS: WOS:000652603700003
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Résumé: In vitro, depending on extracellular matrix (ECM) architecture, macrophages migrate either in amoeboid or mesenchymal mode; while the first is a general trait of leukocytes, the latter is associated with tissue remodelling via Matrix Metalloproteinases (MMPs). To assess whether these stereotyped migrations could be also observed in a physiological context, we used the zebrafish embryo and monitored macrophage morphology, behaviour and capacity to mobilise haematopoietic stem/progenitor cells (HSPCs), as a final functional readout. Morphometric analysis identified 4 different cell shapes. Live imaging revealed that macrophages successively adopt all four shapes as they migrate through ECM. Treatment with inhibitors of MMPs or Rac GTPase to abolish mesenchymal migration, suppresses both ECM degradation and HSPC mobilisation while differently affecting macrophage behaviour. This study depicts real time macrophage behaviour in a physiological context and reveals extreme reactivity of these cells constantly adapting and switching migratory shapes to achieve HSPCs proper mobilisation.
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Physical modeling of the ParBS complex: insight into Liquid-Liquid Phase Separation
Auteur(s): Walter J.-C.
Conférence invité: BioPhyChrom 2021 (The biology and physics of bacterial chromosome organization) (Leiden, NL, 2021-04-29)
Texte intégral en Openaccess :
Ref HAL: hal-03215528_v1
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Résumé: The ParABS system is composed of three components: 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 (ParBS) that serve as substrates for ParA molecules to catalyze positioning and segregation events. We address the theoretical modeling of ParBS with a Lattice Gas models and compare it to experiments [1]. We give evidences that (i) ParBS is formed via a Liquid-Liquid Phase Separation in the metastable region of the phase diagram and (ii) this nucleation is catalyzed with the parS sequence [1].[1] Guilhas, Walter,... & Nollmann (2020). ATP-driven separation of liquid phase condensates in bacteria. Mol. Cell, 79, 293-303.
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