arXiv subjects

Davide Marenduzzo

Publications and source records attributed to Davide Marenduzzo.

At least 37 records · Page 2Linked to original sources

arXiv2024

Bridging-Induced Phase Separation and Loop Extrusion Drive Noise in Chromatin Transcription

Transcriptional noise, or heterogeneity, is important in cellular development and in disease. The molecular mechanisms driving it are, however, elusive and ill-understood. Here, we use computer simulations to explore the role of 3D chromatin structure in driving transcriptional noise. We study a simple polymer model where proteins - modeling complexes of transcription factors and polymerases - bind multivalently to transcription units - modeling regulatory elements such as promoters and enhancers. We also include cohesin-like factors which extrude chromatin loops that are important for the physiological folding of chromosomes. We find that transcription factor binding creates spatiotemporal patterning and a highly variable correlation time in transcriptional dynamics, providing a mechanism for intrinsic noise within a single cell. Instead, loop extrusion contributes to extrinsic noise, as the stochastic nature of this process leads to different networks of cohesin loops in different cells in our simulations. Our results could be tested with single-cell experiments and provide a pathway to understanding the principles underlying transcriptional plasticity in vivo.

physics.bio-ph↗

arXiv2024

Entangled nematic disclinations using multi-particle collision dynamics

Colloids dispersed in nematic liquid crystals form topological composites in which colloid-associated defects mediate interactions while adhering to fundamental topological constraints. Better realising the promise of such materials requires numerical methods that model nematic inclusions in dynamic and complex scenarios. We employ a mesoscale approach for simulating colloids as mobile surfaces embedded in a fluctuating nematohydrodynamic medium to study the kinetics of colloidal entanglement. In addition to reproducing far-field interactions, topological properties of disclination loops are resolved to reveal their metastable states and topological transitions during relaxation towards ground state. The intrinsic hydrodynamic fluctuations distinguish formerly unexplored far-from-equilibrium disclination states, including configurations with localised positive winding profiles. The adaptability and precision of this numerical approach offers promising avenues for studying the dynamics of colloids and topological defects in designed and out-of-equilibrium situations.

cond-mat.soft↗

arXiv2024

3D active nematic disclinations behave as Majorana quasiparticles

Quasiparticles are low-energy excitations with important roles in condensed matter physics. An intriguing example is provided by Majorana fermions, quasiparticles which are identical to their antiparticles. Despite being implicated in neutrino oscillations and topological superconductivity, their experimental realisations remain scarce. Here we propose a purely classical realisation of Majorana fermions, in terms of 3-dimensional disclination lines in active nematics. Activity is required to overcome the elastic cost associated with these excitations, so they can appear in steady state. We combine topology and simulations to show that active nematics under confinement spontaneously create in their interior topologically charged disclination lines and loops, akin to Majorana quasiparticles with finite momentum. Within an elongated channel, we find a phenomenology similar to that of the Kitaev chain, as local Majorana-like excitations appear near surfaces, while a non-local system-spanning helical disclination line can arise along the centre. In unconfined active turbulence, Majorana-like charged loops are instead exceedingly rare, suggesting that boundaries are crucial to generate these quasiparticles, as in quantum condensed matter. We suggest that 3-dimensional active disclinations can be used to probe the physics of Majorana spinors at a much larger scale than traditionally considered, potentially facilitating the experimental observation of their dynamics.

cond-mat.soft↗

arXiv2024

Controlling flow patterns and topology in active emulsions

Active emulsions and liquid crystalline shells are intriguing and experimentally realisable types of topological matter. Here we numerically study the morphology and spatiotemporal dynamics of a double emulsion, where one or two passive small droplets are embedded in a larger active droplet. We find activity introduces a variety of rich and nontrivial nonequilibrium states in the system. First, a double emulsion with a single active droplet becomes self-motile, and there is a transition between translational and rotational motion: both of these regimes remain defect-free, hence topologically trivial. Second, a pair of particles nucleate one or more disclination loops, with conformational dynamics resembling a rotor or chaotic oscillator, accessed by tuning activity. In the first state a single, topologically charged, disclination loop powers the rotation. In the latter state, this disclination stretches and writhes in 3D, continuously undergoing recombination to yield an example of an active living polymer. These emulsions can be self-assembled in the lab, and provide a pathway to form flow and topology patterns in active matter in a controllable way, as opposed to bulk systems that typically yield active turbulence.

cond-mat.soft↗

arXiv2023

Combinatorics and topological weights of chromatin loop networks

Polymer physics models suggest that chromatin spontaneously folds into loop networks with transcription units (TUs), such as enhancers and promoters, as anchors. Here we use combinatoric arguments to enumerate the emergent chromatin loop networks, both in the case where TUs are labelled and where they are unlabelled. We then combine these mathematical results with those of computer simulations aimed at finding the inter-TU energy required to form a target loop network. We show that different topologies are vastly different in terms of both their combinatorial weight and energy of formation. We explain the latter result qualitatively by computing the topological weight of a given network -- i.e., its partition function in statistical mechanics language -- in the approximation where excluded volume interactions are neglected. Our results show that networks featuring local loops are statistically more likely with respect to networks including more non-local contacts. We suggest our classification of loop networks, together with our estimate of the combinatorial and topological weight of each network, will be relevant to catalogue 3D structures of chromatin fibres around eukaryotic genes, and to estimate their relative frequency in both simulations and experiments.

physics.bio-ph↗

arXiv2023

Topological spectra and entropy of chromatin loop networks

The 3D folding of a mammalian gene can be studied by a polymer model, where the chromatin fibre is represented by a semiflexible polymer which interacts with multivalent proteins, representing complexes of DNA-binding transcription factors and RNA polymerases. This physical model leads to the natural emergence of clusters of proteins and binding sites, accompanied by the folding of chromatin into a set of topologies, each associated with a different network of loops. Here we combine numerics and analytics to first classify these networks and then find their relative importance or statistical weight, when the properties of the underlying polymer are those relevant to chromatin. Unlike polymer networks previously studied, our chromatin networks have finite average distances between successive binding sites, and this leads to giant differences between the weights of topologies with the same number of edges and nodes but different wiring. These weights strongly favour rosette-like structures with a local cloud of loops with respect to more complicated non-local topologies. Our results suggest that genes should overwhelmingly fold into a small fraction of all possible 3D topologies, which can be robustly characterised by the framework we propose here.

physics.bio-ph↗

arXiv2023

Motility induced phase separation of deformable cells

Using a multi-phase field model, we examine how particle deformability, which is a proxy for cell stiffness, affects motility induced phase separation (MIPS). We show that purely repulsive deformable, i.e., squishy, cells phase separate more effectively than their rigid counterparts. This can be understood as due to the fact that deformability increases the effective duration of collisions. In addition, the dense regions become increasingly disordered as deformability increases. Our results contextualize the applicability of MIPS to biological systems and have implications for how cells in biological systems may self-organize

cond-mat.soft↗

arXiv2023

Shapes and dynamic regimes of a polar active fluid droplet under confinement

Active droplets are artificial microswimmers built from a liquid dispersion by microfluidic tools and showing self-propelled motion. These systems hold particular interest for mimicking biological phenomena, such as some aspects of cell locomotion and collective behaviors of bacterial colonies, as well as for the design of droplet-based biologically inspired materials, such as engineered tissues. Growing evidence suggests that geometrical confinement crucially affects their morphology and motility, but the driving physical mechanisms are still poorly understood. Here we study the effect of activity on a droplet containing a contractile polar fluid confined within microfluidic channels of various sizes. We find a surprising wealth of shapes and dynamic regimes, whose mechanics is regulated by a subtle interplay between contractile stress, droplet elasticity and microchannel width. They range from worm-like and cell-like shaped droplets displaying an oscillating behavior within wider channels to bullet-shaped droplets exhibiting rectilinear motion in narrower slits. Our findings support the view that geometrical confinement can provide a viable strategy to control and predict the propulsion direction of active droplets. It would be of interest to look for analogues of these motility modes in biological cells or in synthetic active matter.

cond-mat.soft↗

arXiv2023

Topological Phases and Curvature-Driven Pattern Formation in Cholesteric Shells

We study the phase behaviour of cholesteric liquid crystal shells with different geometries. We compare the cases of tangential and no anchoring at the surface, focussing on the former case, which leads to a competition between the intrinsic tendency of the cholesteric to twist and the anchoring free energy which suppresses it. We then characterise the topological phases arising close to the isotropic-cholesteric transition. These typically consist of quasi-crystalline or amorphous tessellations of the surface by half-skyrmions, which are stable at lower and larger shell size respectively. For ellipsoidal shells, defects in the tessellation couple to local curvature, and according to the shell size they either migrate to the poles or distribute uniformly on the surface. For toroidal shells, the variations in the local curvature of the surface stabilises heterogeneous phases where cholesteric or isotropic patterns coexist with hexagonal lattices of half-skyrmions.

cond-mat.soft↗

arXiv2022

Active turbulence and spontaneous phase separation in inhomogeneous extensile active gels

We report numerical results for the hydrodynamics of inhomogeneous lyotropic and extensile active nematic gels. By simulating the coupled Cahn-Hilliard, Navier-Stokes, and Beris-Edwards equation for the evolution of the composition, flow and orientational order of an active nematic, we ask whether composition variations are important to determine its emergent physics. As in active gels of uniform composition, we find that increasing either activity or nematic tendency (e.g., overall active matter concentration) triggers a transition between an isotropic passive phase and an active nematic one. We show that composition inhomogeneities are important in the latter phase, where we find three types of possible dynamical regimes. First, we observe regular patterns with defects and vortices: these exist close to the passive-active transition. Second, for larger activity, or deeper in the nematic phase, we find active turbulence, as in active gels of uniform composition, but with exceedingly large composition variation. In the third regime, which is uniquely associated with inhomogeneity and occurs for large nematic tendency and low activity, we observe spontaneous microphase separation into active and passive domains. The microphase separated regime is notable in view of the absence of an explicit demixing term in the underlying free energy which we use, and we provide a theoretical analysis based on the common tangent construction which explains its existence. We hope this regime can be probed experimentally in the future.

cond-mat.soft↗

arXiv2022

3D polymer simulations of genome organization and transcription across different chromosomes and cell types

We employ the diffusing transcription factors model for numerical simulation of chromatin topology conformations and transcriptional processes of human chromatin. Simulations of a short chromatin filament reveal different possible pathways to regulate transcription: it is shown that the transcriptional activity profile can be regulated and controlled by either acting on the chain structural properties, or on external factors, such as the number of transcription factors. Additionally, comparisons between GRO-seq experimental data and large scale numerical simulation of entire chromosomes from the human umbilical vein endothelial cell and the B-lmphocyte GM12878 show that the model provides reliable and statistically significant predictions for transcription across different cell-lines.

cond-mat.soft↗

arXiv2022

Yield-stress transition in suspensions of deformable droplets

Yield-stress materials, which require a sufficiently large forcing to flow, are currently ill-understood theoretically. To gain insight into their yielding transition, here we study numerically the rheology of a suspension of deformable droplets under pressure-driven flow. We show that the suspension displays yield-stress behaviour, with the droplets remaining motionless when the applied body-force is below a critical value. In the non-flowing phase, droplets jam to form an amorphous structure, whereas they order in the flowing phase. Yielding is linked to a percolation transition in the contacts of droplet-droplet overlaps, and requires suitable wetting boundary conditions and strict conservation of the droplet area to exist. Close to the yielding transition, we find strong oscillations in the droplet motion which closely resemble those found experimentally in confined colloidal glasses under flow. We show that even when droplets are static the underlying solvent moves by permeation, so that the viscosity of the composite system is never truly infinite, and, as we discuss, its precise value ceases to be a bulk material property of the system.

cond-mat.soft↗

arXiv2022

Yield Stress and Compliance in Active Cell Monolayers

The rheology of biological tissue plays an important role in many processes, from organ formation to cancer invasion. Here, we use a multi-phase field model of motile cells to simulate active microrheology within a tissue monolayer. When unperturbed, the tissue exhibits a transition between a solid-like state and a fluid-like state tuned by cell motility and deformability - the ratio of the energetic costs of steric cell-cell repulsion and cell surface tension. When perturbed, solid tissues exhibit yield-stress behavior, with a threshold force for the onset of motion of a probe particle that vanishes upon approaching the solid-to-liquid transition. This onset of motion is qualitatively different in the low and high deformability regimes. At high deformability, the tissue is amorphous when solid, it responds compliantly to deformations, and the probe transition to motion is smooth. At low deformability, the monolayer is more ordered translationally and stiffer, and the onset of motion appears discontinuous. Our results suggest that cellular or nanoparticle transport in different types of tissues can be fundamentally different, and point to ways in which it can be controlled.

cond-mat.soft↗

arXiv2021

Cholesteric shells: two-dimensional blue fog and finite quasicrystals

We study the phase behaviour of a quasi-two dimensional cholesteric liquid crystal shell. We characterise the topological phases arising close to the isotropic-cholesteric transition, and show that they differ in a fundamental way from those observed on a flat geometry. For spherical shells, we discover two types of quasi-two dimensional topological phases: finite quasicrystals and amorphous structures, both made up by mixtures of polygonal tessellations of half-skyrmions. These structures generically emerge instead of regular double twist lattices because of geometric frustration, which disallows a regular hexagonal tiling of curved space. For toroidal shells, the variations in the local curvature of the surface stabilises heterogeneous phases where cholesteric patterns coexist with hexagonal lattices of half-skyrmions. Quasicrystals, amorphous and heterogeneous structures could be sought experimentally by self assembling cholesteric shells on the surface of emulsion droplets.

cond-mat.soft↗

arXiv2021

A renormalization group study of the dynamics of active membranes: universality classes and scaling laws

Motivated by experimental observations of patterning at the leading edge of motile eukaryotic cells, we introduce a general model for the dynamics of nearly-flat fluid membranes driven from within by an ensemble of activators. We include, in particular, a kinematic coupling between activator density and membrane slope which generically arises whenever the membrane has a non-vanishing normal speed. We unveil the phase diagram of the model by means of a perturbative field-theoretical renormalization group analysis. Due to the aforementioned kinematic coupling the natural dynamical scaling is acoustic, that is the dynamical critical exponent is 1. However, as soon as the the normal velocity of the membrane is tuned to zero, the system crosses over to diffusive dynamic scaling in mean field. Distinct critical points can be reached depending on how the limit of vanishing velocity is realised: in each of them corrections to scaling due to nonlinear coupling terms must be taken into accounts. The detailed analysis of these critical points reveals novel scaling regimes wich can be accessed with perturbative methods, together with signs of strong coupling behaviour, which establishes a promising ground for further non-perturbative calculations. Our results unify several previous studies on the dynamics of active membrane, while also identifying nontrivial scaling regimes which cannot be captured by passive theories of fluctuating interfaces and are relevant for the physics of living membranes.

cond-mat.stat-mech↗

arXiv2021

Universal properties of active membranes

We put forward a general field theory for membranes with embedded activators and analyse their critical properties using renormalization group techniques. Depending on the membrane-activator coupling, we find a crossover between acoustic and diffusive scaling regimes, with mean-field dynamical critical exponents z = 1 and 2 respectively. We argue that the acoustic scaling, which is exact in all spatial dimensions, is a suitable candidate for the universal description of the spatiotemporal patterns observed at the leading edge of motile cells. Furthermore, one-loop corrections to the diffusive mean-field exponents reveal universal behaviour distinct from the Kardar-Parisi-Zhang scaling of passive interfaces and signs of strong-coupling behaviour.

cond-mat.stat-mech↗

arXiv2020

Simplifying Topological Entanglements by Entropic Competition of Slip-Links

Topological entanglements are abundant, and often detrimental, in polymeric systems in biology and materials science. Here we theoretically investigate the topological simplification of knots by diffusing slip-links (SLs), which may represent biological or synthetic molecules, such as proteins on the genome or cyclodextrines in slide-ring gels. We find that SLs entropically compete with knots and can localise them, greatly facilitating their downstream simplification by transient strand-crossing. We further show that the efficiency of knot localisation strongly depends on the topology of the SL network and, informed by our findings, discuss potential strategies to control the topology of biological and synthetic materials.

cond-mat.soft↗

arXiv2020

Chromosome Compaction and Chromatin Stiffness Enhance Diffusive Loop Extrusion by Slip-Link Proteins

We use Brownian dynamics simulations to study the formation of chromatin loops through diffusive sliding of slip-link-like proteins, mimicking the behaviour of cohesin molecules. We recently proposed that diffusive sliding is sufficient to explain the extrusion of chromatin loops of hundreds of kilo-base-pairs (kbp), which may then be stabilised by interactions between cohesin and CTCF proteins. Here we show that the flexibility of the chromatin fibre strongly affects this dynamical process, and find that diffusive loop extrusion is more efficient on stiffer chromatin regions. We also show that the dynamics of loop formation are faster in confined and collapsed chromatin conformations but that this enhancement is counteracted by the increased crowding. We provide a simple theoretical argument explaining why stiffness and collapsed conformations favour diffusive extrusion. In light of the heterogeneous physical and conformational properties of eukaryotic chromatin, we suggest that our results are relevant to understand the looping and organisation of interphase chromosomes in vivo.

cond-mat.soft↗