Université PSL

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RECHERCHER

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Large work extraction and the Landauer limit in a continuous Maxwell demon
Marco Ribezzi Crivellari
Nature Physics - 15(7) 93 - DOI: 10.1038/s41567-019-0481-0 - 2019
The relation between entropy and information dates back to the classical Maxwell demon paradox¹, a thought experiment proposed in 1867 by James Clerk Maxwell to violate the second law of thermodynamics. A variant of the classical Maxwell demon is the Szilard engine, proposed by Leo Szilard in 1929¹. In it, at a given time, the demon observes the compartment occupied by a single molecule in a vessel and extracts work by operating a pulley device. Here, we introduce the continuous Maxwell demon, a device capable of extracting arbitrarily large amounts of work per cycle by repeated measurements of the state of a system, and experimentally test it in single DNA hairpin pulling experiments. In the continuous Maxwell demon, the demon monitors the state of the DNA hairpin (folded or unfolded) by observing it at equally spaced time intervals, but it extracts work only when the molecule changes state. We demonstrate that the average maximum work per cycle that can be extracted by the continuous Maxwell demon is limited by the information content of the stored sequences, in agreement with the second law. Work extraction efficiency is found to be maximal in the large information-content limit where work extraction is fuelled by rare events.
High-throughput single-cell ChIP-seq identifies heterogeneity of chromatin states in breast cancer
Grosselin K1,2,3, Durand A4,5, Marsolier J, Poitou A, Marangoni E, Nemati F, Dahmani A, Lameiras S, Reyal F, Frenoy O, Pousse Y, Reichen M, Woolfe A, Brenan C, Griffiths AD, Vallot C, Gérard A.i
Nat Genet. - 51(6) 1060-1066 - doi: 10.1038/s41588-019-0424-9. - 2019
Modulation of chromatin structure via histone modification is a major epigenetic mechanism and regulator of gene expression. However, the contribution of chromatin features to tumor heterogeneity and evolution remains unknown. Here we describe a high-throughput droplet microfluidics platform to profile chromatin landscapes of thousands of cells at single-cell resolution. Using patient-derived xenograft models of acquired resistance to chemotherapy and targeted therapy in breast cancer, we found that a subset of cells within untreated drug-sensitive tumors share a common chromatin signature with resistant cells, undetectable using bulk approaches. These cells, and cells from the resistant tumors, have lost chromatin marks-H3K27me3, which is associated with stable transcriptional repression-for genes known to promote resistance to treatment. This single-cell chromatin immunoprecipitation followed by sequencing approach paves the way to study the role of chromatin heterogeneity, not just in cancer but in other diseases and healthy systems, notably during cellular differentiation and development.
Experimental evidence of symmetry breaking of transition-path times
J.Gladrow, M. Ribezzi-Crivellari, F. Ritort & U. F. Keyser
Nature Communications - 10 55 - doi.org/10.1038/s41467-018-07873-9 - 2019
While thermal rates of state transitions in classical systems have been studied for almost a century, associated transition-path times have only recently received attention. Uphill and downhill transition paths between states at different free energies should be statistically indistinguishable. Here, we systematically investigate transition-path-time symmetry and report evidence of its breakdown on the molecular- and meso-scale out of equilibrium. In automated Brownian dynamics experiments, we establish first-passage-time symmetries of colloids driven by femtoNewton forces in holographically-created optical landscapes confined within microchannels. Conversely, we show that transitions which couple in a path-dependent manner to fluctuating forces exhibit asymmetry. We reproduce this asymmetry in folding transitions of DNA-hairpins driven out of equilibrium and suggest a topological mechanism of symmetry breakdown. Our results are relevant to measurements that capture a single coordinate in a multidimensional free energy landscape, as encountered in electrophysiology and single-molecule fluorescence experiments.
Recent insights into the genotype–phenotype relationship from massively parallel genetic assays
Harry Kemble Philippe Nghe Olivier Tenaillon
Nature Physics - 9 12 - doi.org/10.1111/eva.12846 - 2019
With the molecular revolution in Biology, a mechanistic understanding of the genotype–phenotype relationship became possible. Recently, advances in DNA synthesis and sequencing have enabled the development of deep mutational scanning assays, capable of scoring comprehensive libraries of genotypes for fitness and a variety of phenotypes in massively parallel fashion. The resulting empirical genotype–fitness maps pave the way to predictive models, potentially accelerating our ability to anticipate the behaviour of pathogen and cancerous cell populations from sequencing data. Besides from cellular fitness, phenotypes of direct application in industry (e.g. enzyme activity) and medicine (e.g. antibody binding) can be quantified and even selected directly by these assays. This review discusses the technological basis of and recent developments in massively parallel genetics, along with the trends it is uncovering in the genotype–phenotype relationship (distribution of mutation effects, epistasis), their possible mechanistic bases and future directions for advancing towards the goal of predictive genetics.
Large scale control and programming of gene expression using CRISPR.
Deyell M, Ameta S, Nghe P
Semin Cell Dev Biol. - S1084-9521(18 30110-1 - doi: 10.1016/j.semcdb.2019.05.013 - 2019
The control of gene expression in cells and organisms allows to unveil gene to function relationships and to reprogram biological responses. Several systems, such as Zinc fingers, TALE (Transcription activator-like effectors), and siRNAs (small-interfering RNAs), have been exploited to achieve this. However, recent advances in Clustered Regularly Interspaced Short Palindromic Repeats and Cas9 (CRISPR-Cas9) have overshadowed them due to high specificity, compatibility with many different organisms, and design flexibility. In this review we summarize state-of-the art for CRISPR-Cas9 technology for large scale gene perturbation studies, including single gene and multiple genes knock-out, knock-down, knock-up libraries, and their associated screening assays. We feature in particular the combination of these methods with single-cell transcriptomics approaches. Finally, we highlight the application of CRISPR-Cas9 systems in building synthetic circuits that can be interfaced with gene networks to control cellular states.
Large scale control and programming of gene expression using CRISPR.
Deyell M, Ameta S, Nghe P
Semin Cell Dev Biol. - S1084-9521(18 30110-1 - doi: 10.1016/j.semcdb.2019.05.013 - 2019
The control of gene expression in cells and organisms allows to unveil gene to function relationships and to reprogram biological responses. Several systems, such as Zinc fingers, TALE (Transcription activator-like effectors), and siRNAs (small-interfering RNAs), have been exploited to achieve this. However, recent advances in Clustered Regularly Interspaced Short Palindromic Repeats and Cas9 (CRISPR-Cas9) have overshadowed them due to high specificity, compatibility with many different organisms, and design flexibility. In this review we summarize state-of-the art for CRISPR-Cas9 technology for large scale gene perturbation studies, including single gene and multiple genes knock-out, knock-down, knock-up libraries, and their associated screening assays. We feature in particular the combination of these methods with single-cell transcriptomics approaches. Finally, we highlight the application of CRISPR-Cas9 systems in building synthetic circuits that can be interfaced with gene networks to control cellular states.
Innate control of actin nucleation determines two distinct migration behaviours in dendritic cells.
Vargas P, Maiuri P, Bretou M, Sáez PJ, Pierobon P, Maurin M, Chabaud M, Lankar D, Obino D, Terriac E, Raab M, Thiam H-R, Brocker T, Kitchen-Goosen SM, Alberts AS, Sunareni P, Xia S, Li R, Voituriez R, Piel M, Lennon-Duménil A-M
Nat. Cell Biol. - 18(1): 43-53 - DOI: 10.1016/j.jim.2015.12.005 - 2019
Dendritic cell (DC) migration in peripheral tissues serves two main functions: antigen sampling by immature DCs, and chemokine-guided migration towards lymphatic vessels (LVs) on maturation. These migratory events determine the efficiency of the adaptive immune response. Their regulation by the core cell locomotion machinery has not been determined. Here, we show that the migration of immature DCs depends on two main actin pools: a RhoA-mDia1-dependent actin pool located at their rear, which facilitates forward locomotion; and a Cdc42-Arp2/3-dependent actin pool present at their front, which limits migration but promotes antigen capture. Following TLR4-MyD88-induced maturation, Arp2/3-dependent actin enrichment at the cell front is markedly reduced. Consequently, mature DCs switch to a faster and more persistent mDia1-dependent locomotion mode that facilitates chemotactic migration to LVs and lymph nodes. Thus, the differential use of actin-nucleating machineries optimizes the migration of immature and mature DCs according to their specific function.
Optical volume and mass measurements show that mammalian cells swell during mitosis.
Zlotek-Zlotkiewicz E, Monnier S, Cappello G, Le Berre M, Piel M
J. Cell Biol. - 211( 4): 765-74 - DOI: 10.1016/j.jim.2015.12.005 - 2019
The extent, mechanism, and function of cell volume changes during specific cellular events, such as cell migration and cell division, have been poorly studied, mostly because of a lack of adequate techniques. Here we unambiguously report that a large range of mammalian cell types display a significant increase in volume during mitosis (up to 30%). We further show that this increase in volume is tightly linked to the mitotic state of the cell and not to its spread or rounded shape and is independent of the presence of an intact actomyosin cortex. Importantly, this volume increase is not accompanied by an increase in dry mass and thus corresponds to a decrease in cell density. This mitotic swelling might have important consequences for mitotic progression: it might contribute to produce strong pushing forces, allowing mitotic cells to round up; it might also, by lowering cytoplasmic density, contribute to the large change of physicochemical properties observed in mitotic cells.
Actin Flows Mediate a Universal Coupling between Cell Speed and Cell Persistence.
Maiuri P, Rupprecht J-F, Wieser S, Ruprecht V, Bénichou O, Carpi N, Coppey M, De Beco S, Gov N, Heisenberg C-P, Lage Crespo C, Lautenschlaeger F, Le Berre M, Lennon-Dumenil A-M, Raab M, Thiam H-R, Piel M, Sixt M, Voituriez R
Cell - 161(2) 374-86 - DOI: 10.1016/j.cell.2015.01.056 - 2019
Cell movement has essential functions in development, immunity, and cancer. Various cell migration patterns have been reported, but no general rule has emerged so far. Here, we show on the basis of experimental data in vitro and in vivo that cell persistence, which quantifies the straightness of trajectories, is robustly coupled to cell migration speed. We suggest that this universal coupling constitutes a generic law of cell migration, which originates in the advection of polarity cues by an actin cytoskeleton undergoing flows at the cellular scale. Our analysis relies on a theoretical model that we validate by measuring the persistence of cells upon modulation of actin flow speeds and upon optogenetic manipulation of the binding of an actin regulator to actin filaments. Beyond the quantitative prediction of the coupling, the model yields a generic phase diagram of cellular trajectories, which recapitulates the full range of observed migration patterns.
Deterministic patterns in cell motility
Ido Lavi, Matthieu Piel, Ana-Maria Lennon-Duménil , Raphaël Voituriez and Nir S. Gov
Nature Physics - 12 1146–1152 - DOI: : 10.1038/NPHYS3836 - 2019
Cell migration paths are generally described as random walks, associated with both intrinsic and extrinsic noise. However, complex cell locomotion is not merely related to such fluctuations, but is often determined by the underlying machinery. Cell motility is driven mechanically by actin and myosin, two molecular components that generate contractile forces. Other cell functions make use of the same components and, therefore, will compete with the migratory apparatus. Here, we propose a physical model of such a competitive system, namely dendritic cells whose antigen capture function and migratory ability are coupled by myosin II. The model predicts that this coupling gives rise to a dynamic instability, whereby cells switch from persistent migration to unidirectional self-oscillation, through a Hopf bifurcation. Cells can then switch to periodic polarity reversals through a homoclinic bifurcation. These predicted dynamic regimes are characterized by robust features that we identify through in vitro trajectories of dendritic cells over long timescales and distances. We expect that competition for limited resources in other migrating cell types can lead to similar deterministic migration modes.

396 publications.