Rings in Random Environments: Sensing Disorder Through Topology

In this paper we study the role of topology in DNA gel electrophoresis experiments via molecular dynamics simulations. The gel is modelled as a 3D array of obstacles from which half edges are removed at random with probability p, thereby generating a disordered environment. Changes in the microscopic structure of the gel are captured by measuring the electrophoretic mobility of ring polymers moving through the medium, while their linear counterparts provide a control system as we show they are insensitive to these changes. We show that ring polymers provide a novel non-invasive way of exploiting topology to sense microscopic disorder. Finally, we compare the results from the simulations with an analytical model for the non-equilibrium differential mobility, and find a striking agreement between simulation and theoryComment: 8 pages,6 figures Accepted for publication in Soft Matte

Separation of Geometrical and Topological Entanglement in Confined Polymers Driven Out-Of-Equilibrium

We use Brownian dynamics simulations and advanced topological profiling methods to characterize the out-of-equilibrium evolution of self-entanglement in linear polymers confined into nanochannels and under periodic compression. By introducing suitable observables, we can distinguish two main forms of entanglement that we term geometrical and topological. The latter is measured by the number of (essential) crossings of the physical knot detected after a suitable bridging of the chain termini. The former is instead measured as the average number of times a linear chain appears to cross itself when viewed under all projections and is irrespective of the physical knotted state. The key discovery of our work is that these two forms of entanglement are uncoupled and evolve with distinct dynamics. While geometrical entanglement is typically in phase with the compression-elongation cycles and it is primarily sensitive to its force f, the topological measure is mildly sensitive to cyclic modulation but strongly depends on both compression force f and duration k. The findings could assist the interpretation of experiments using fluorescence molecular tracers to track physical knots in polymers. Furthermore, we identify optimal regions in the experimentally controllable parameter space in which to obtain more/less topological and geometrical entanglement; this may help designing polymers with targeted topology

Threading-Induced Dynamical Transition in Tadpole-Shaped Polymers

The relationship between polymer topology and bulk rheology remains a key question in soft matter physics. Architecture-specific constraints (or threadings) are thought to control the dynamics of ring polymers in ring-linear blends, which thus affects the viscosity to range between that of the pure rings and a value larger, but still comparable to, that of the pure linear melt. Here we consider qualitatively different systems of linear and ring polymers, fused together in "chimeric" architectures. The simplest example of this family is a "tadpole"-shaped polymer - a single ring fused to the end of a single linear chain. We show that polymers with this architecture display a threading-induced dynamical transition that substantially slows chain relaxation. Our findings shed light on how threadings control dynamics and may inform design principles for chimeric polymers with topologically-tunable bulk rheological properties.Comment: Accepted in ACS Macroletter

A topologically driven glass in ring polymers

The static and dynamic properties of ring polymers in concentrated solutions remains one of the last deep unsolved questions in polymer physics. At the same time, the nature of the glass transition in polymeric systems is also not well understood. In this work, we study a novel glass transition in systems made of circular polymers by exploiting the topological constraints that are conjectured to populate concentrated solutions of rings. We show that such rings strongly interpenetrate through one another, generating an extensive network of topological interactions that dramatically affects their dynamics. We show that a kinetically arrested state can be induced by randomly pinning a small fraction of the rings. This occurs well above the classical glass transition temperature at which microscopic mobility is lost. Our work both demonstrates the existence of long-lived inter-ring penetrations and realizes a novel, topologically induced, glass transition

Integrating transposable elements in the 3D genome

Chromosome organisation is increasingly recognised as an essential component of genome regulation, cell fate and cell health. Within the realm of transposable elements (TEs) however, the spatial information of how genomes are folded is still only rarely integrated in experimental studies or accounted for in modelling. Whilst polymer physics is recognised as an important tool to understand the mechanisms of genome folding, in this commentary we discuss its potential applicability to aspects of TE biology. Based on recent works on the relationship between genome organisation and TE integration, we argue that existing polymer models may be extended to create a predictive framework for the study of TE integration patterns. We suggest that these models may offer orthogonal and generic insights into the integration profiles (or "topography") of TEs across organisms. In addition, we provide simple polymer physics arguments and preliminary molecular dynamics simulations of TEs inserting into heterogeneously flexible polymers. By considering this simple model, we show how polymer folding and local flexibility may generically affect TE integration patterns. The preliminary discussion reported in this commentary is aimed to lay the foundations for a large-scale analysis of TE integration dynamics and topography as a function of the three-dimensional host genome

Threading Dynamics of Ring Polymers in a Gel

We perform large scale three-dimensional molecular dynamics simulations of unlinked and unknotted ring polymers diffusing through a background gel, here a three-dimensional cubic lattice. Taking advantage of this architecture, we propose a new method to unambiguously identify and quantify inter-ring threadings (penetrations) and to relate these to the dynamics of the ring polymers. We find that both the number and the persistence time of the threadings increase with the length of the chains, ultimately leading to a percolating network of inter-ring penetrations. We discuss the implications of these findings for the possible emergence of a topological jammed state of very long rings.Comment: 6 pages, 4 figure

Die Bedeutung von Rhamnolipiden in der Pathogenese epithelialer Pseudomonas aeruginosa Infektionen

Pseudomonas aeruginosa (P. aeruginosa) ist ein ubiquitär vorkommendes, gramnegatives, monotrich begeißeltes, aerob lebendes Stäbchenbakterium. Das opportunistisches Pathogen befällt Menschen, Tiere, Insekten, Nematoden und Pflanzen und ist unter anderem aufgrund seiner Toleranz gegenüber einer Vielzahl von Desinfektionsmitteln und Antibiotika einer der wichtigsten Verursacher von nosokomialen Infektionen. Die Ergebnisse dieser Arbeit geben einen Hinweis darauf, dass P. aeruginosa das angeborene Immunsystem mit Hilfe von Rhamnolipid, einem vom Bakterium selbst produzierten Surfactant, umgeht. In der vorliegenden Arbeit konnte nachgewiesen werden, dass die Flagellin-induzierte hBD2-Expression in humanen Keratinozyten durch bakterielle Überstände von P. aeruginosa, die in der stationären Phase generiert wurden, supprimiert wird. Der supprimierende Faktor konnte in Versuchen als hitzestabil und durch Säure ausfällbar identifiziert werden. Außerdem blieb er bei Behandlung mit Proteinase K unbeeinflusst, es handelt sich deshalb nicht um ein Protein. Weitere Untersuchungen konnten den Faktor als Rhamnolipid identifizieren. Eine Kostimulation von Keratinozyten mit aufgereinigtem Rhamnolipid in Mengen unterhalb der zytotoxischen Konzentration zusammen mit Flagellin zeigte ebenfalls eine Supprimierung der induzierten hBD2-Expression. Ähnliche Effekte konnten bei Kostimulation der Keratinozyten mit Flagellin und BAPTA-AM, einem intrazellulären Calciumchelator, erreicht werden. Neben Flagellin als Induktor ließ sich auch die PMA-induzierte hBD2-Expression supprimieren. Dies lässt vermuten, dass Rhamnolipide mit Calcium-abhängigen Signalkaskaden, wie der PKC-Signalkaskade, interferieren. Die Versuche dieser Arbeit zeigen damit einen Weg, über den es P. aeruginosa möglich ist, sich auf der Haut zu etablieren, ohne seinen Hauptpathogenitätsfaktor, das Flagellin, verstecken zu müssen

oncological outcome of fat grafting for breast reconstruction after cancer

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Simulating topological domains in human chromosomes with a fitting-free model

We discuss a polymer model for the 3D organization of human chromosomes. A chromosome is represented by a string of beads, with each bead being "colored" according to 1D bioinformatic data (e.g., chromatin state, histone modification, GC content). Individual spheres (representing bi- and multi-valent transcription factors) can bind reversibly and selectively to beads with the appropriate color. During molecular dynamics simulations, the factors bind, and the string spontaneously folds into loops, rosettes, and topologically-associating domains (TADs). This organization occurs in the absence of any specified interactions between distant DNA segments, or between transcription factors. A comparison with Hi-C data shows that simulations predict the location of most boundaries between TADs correctly. The model is "fitting-free" in the sense that it does not use Hi-C data as an input; consequently, one of its strengths is that it can - in principle - be used to predict the 3D organization of any region of interest, or whole chromosome, in a given organism, or cell line, in the absence of existing Hi-C data. We discuss how this simple model might be refined to include more transcription factors and binding sites, and to correctly predict contacts between convergent CTCF binding sites