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Callan-Jones A.C.,University Paris Diderot | Voituriez R.,CNRS Jean Perrin Laboratory
Current Opinion in Cell Biology | Year: 2016

Eukaryotic cell movement is characterized by very diverse migration modes. Recent studies show that cells can adapt to environmental cues, such as adhesion and geometric confinement, thereby readily switching their mode of migration. Among this diversity of motile behavior, actin flows have emerged as a highly conserved feature of both mesenchymal and amoeboid migration, and have also been identified as key regulators of cell polarity. This suggests that the various observed migration modes are continuous variations of elementary locomotion mechanisms, based on a very robust physical property of the actin/myosin system - its ability to sustain flows at the cell scale. This central role of actin/myosin flows is shown to affect the large scale properties of cell trajectories. © 2016 Elsevier Ltd.

Chupeau M.,CNRS Laboratory of Theoretical Physics and Condensed Matter | Benichou O.,CNRS Laboratory of Theoretical Physics and Condensed Matter | Voituriez R.,CNRS Laboratory of Theoretical Physics and Condensed Matter | Voituriez R.,CNRS Jean Perrin Laboratory
Nature Physics | Year: 2015

How long must one undertake a random search to visit all sites of a given domain? This time, known as the cover time, is a key observable to quantify the efficiency of exhaustive searches, which require a complete exploration of an area and not only the discovery of a single target. Examples range from immune-system cells chasing pathogens to animals harvesting resources, from robotic exploration for cleaning or demining to the task of improving search algorithms. Despite its broad relevance, the cover time has remained elusive and so far explicit results have been scarce and mostly limited to regular random walks. Here we determine the full distribution of the cover time for a broad range of random search processes, including Lévy strategies, intermittent strategies, persistent random walks and random walks on complex networks, and reveal its universal features. We show that for all these examples the mean cover time can be minimized, and that the corresponding optimal strategies also minimize the mean search time for a single target, unambiguously pointing towards their robustness. © 2015 Macmillan Publishers Limited. All rights reserved.

Hernandez B.,University of Paris 13 | Pfluger F.,University of Paris 13 | Lopez-Tobar E.,CSIC - Institute for the Structure of Matter | Kruglik S.G.,Paris-Sorbonne University | And 4 more authors.
Journal of Raman Spectroscopy | Year: 2014

During the last decades, Raman spectroscopy has been routinely used for probing the conformational features of disulfide linkages in peptides and proteins. However, the interpretation of disulfide Raman markers is currently performed by a simple rule derived from the earliest observations on dialkyl disulfides. More precisely, this rule consists of the following: (1) in analyzing the Raman bands in the 550-500 cm-1 region ascribed to disulfide bond stretch motion, namely, ν(S-S), and (2) assigning the three types of Raman markers observed at ~500, ~520, and ~540 cm-1 to three families of rotamers defined along the three successive bonds of the -C-S-S-C- moiety, referred to as ggg, ggt, and tgt. In this report, we attempt to show that an accurate analysis of disulfide vibrational features needs the use of the five torsion angles (χ1, χ2, χ3, χ2', and χ1') along the five successive bonds joining the two α-carbon atoms in the cystine (Cys-Cys) unit. The present work is inspired by the disulfide conformational investigations performed by a statistical scan of numerous protein crystal and nuclear magnetic resonance data, taking into account the handedness (right and left) of a disulfide bridge, its spatial shape (Staple, Hook, and Spiral), as well as the signs of the two extreme torsion angles χ1 and χ1'. It appears that the combined use of the old and recent conformational notations allows a more accurate structural and vibrational analysis of disulfide linkage. Copyright © 2014 John Wiley & Sons, Ltd. It has been shown that the old notations (ggg, ggt, and tgt) are insufficient for analyzing the conformational and vibrational features of disulfide linkages in peptides and proteins. This failure can be improved by considering the new topological notations based on the signs of the five torsion angles in going from one α-carbon to the other in the cystine unit. Copyright © 2014 John Wiley & Sons, Ltd.

Ke R.,University of California at Los Angeles | Ke R.,Los Alamos National Laboratory | Loverdo C.,University of California at Los Angeles | Loverdo C.,CNRS Jean Perrin Laboratory | And 6 more authors.
PLoS Computational Biology | Year: 2015

Recent discoveries of direct acting antivirals against Hepatitis C virus (HCV) have raised hopes of effective treatment via combination therapies. Yet rapid evolution and high diversity of HCV populations, combined with the reality of suboptimal treatment adherence, make drug resistance a clinical and public health concern. We develop a general model incorporating viral dynamics and pharmacokinetics/ pharmacodynamics to assess how suboptimal adherence affects resistance development and clinical outcomes. We derive design principles and adaptive treatment strategies, identifying a high-risk period when missing doses is particularly risky for de novo resistance, and quantifying the number of additional doses needed to compensate when doses are missed. Using data from large-scale resistance assays, we demonstrate that the risk of resistance can be reduced substantially by applying these principles to a combination therapy of daclatasvir and asunaprevir. By providing a mechanistic framework to link patient characteristics to the risk of resistance, these findings show the potential of rational treatment design. © 2015 Ke et al.

Maiuri P.,University Pierre and Marie Curie | Rupprecht J.-F.,CNRS Laboratory of Theoretical Physics and Condensed Matter | Wieser S.,AM Technology | Ruprecht V.,AM Technology | And 16 more authors.
Cell | Year: 2015

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. © 2015 Elsevier Inc.

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