Active motion of tangentially driven polymers in periodic array of obstacles.

One key question about transport of active polymers within crowded environments is how spatial order of obstacles influences their conformation and dynamics when compared to disordered media. To this end, we computationally investigate the active transport of tangentially driven polymers with varying degrees of flexibility and activity in two-dimensional square lattices of obstacles. Tight periodic confinement induces notable conformational changes and distinct modes of transport for flexible and stiff active filaments. It leads to caging of low activity flexible polymers inside the inter-obstacle pores while promoting more elongated conformations and enhanced diffusion for stiff polymers at low to moderate activity levels. The migration of flexible active polymers occurs via hopping events, where they unfold to move from one cage to another, similar to their transport in disordered media. However, in ordered media, polymers are more compact and their long-time dynamics is significantly slower. In contrast, stiff chains travel mainly in straight paths within periodic inter-obstacle channels while occasionally changing their direction of motion. This mode of transport is unique to periodic environment and leads to more extended conformation and substantially enhanced long-time dynamics of stiff filaments with low to moderate activity levels compared to disordered media. At high active forces, polymers overcome confinement effects and move through inter-obstacle pores just as swiftly as in open spaces, regardless of the spatial arrangement of obstacles. We explain the center of mass dynamics of semiflexible polymers in terms of active force and obstacle packing fraction by developing an approximate analytical theory.

Effects of inertia on conformation and dynamics of tangentially driven active filaments.

Active filamentlike systems propelling along their backbone exist across scales ranging from motor-driven biofilaments to worms and robotic chains. In macroscopic active filaments such as a chain of robots, in contrast to their microscopic counterparts, inertial effects on their motion cannot be ignored. Nonetheless, the consequences of the interplay between inertia and flexibility on the shape and dynamics of active filaments remain unexplored. Here we examine inertial effects on a flexible tangentially driven active polymer model pertinent to the above examples and we determine the conditions under which inertia becomes important. Performing Langevin dynamics simulations of active polymers with underdamped and overdamped dynamics for a wide range of contour lengths and activities, we uncover striking inertial effects on conformation and dynamics for high levels of activities. Inertial collisions increase the persistence length of active polymers and remarkably alter their scaling behavior. In stark contrast to passive polymers, inertia leaves its fingerprint at long times by an enhanced diffusion of the center of mass. We rationalize inertia-induced enhanced dynamics by analytical calculations of center-of-mass velocity correlations, applicable to any active polymer model, which reveal significant contributions from active force fluctuations convoluted by inertial relaxation.

Loop-extrusion and polymer phase-separation can co-exist at the single-molecule level to shape chromatin folding.

Loop-extrusion and phase-separation have been proposed as mechanisms that shape chromosome spatial organization. It is unclear, however, how they perform relative to each other in explaining chromatin architecture data and whether they compete or co-exist at the single-molecule level. Here, we compare models of polymer physics based on loop-extrusion and phase-separation, as well as models where both mechanisms act simultaneously in a single molecule, against multiplexed FISH data available in human loci in IMR90 and HCT116 cells. We find that the different models recapitulate bulk Hi-C and average multiplexed microscopy data. Single-molecule chromatin conformations are also well captured, especially by phase-separation based models that better reflect the experimentally reported segregation in globules of the considered genomic loci and their cell-to-cell structural variability. Such a variability is consistent with two main concurrent causes: single-cell epigenetic heterogeneity and an intrinsic thermodynamic conformational degeneracy of folding. Overall, the model combining loop-extrusion and polymer phase-separation provides a very good description of the data, particularly higher-order contacts, showing that the two mechanisms can co-exist in shaping chromatin architecture in single cells.

Dynamics of Bacteria Scanning a Porous Environment.

It has recently been reported that bacteria, such as Escherichia coli Bhattacharjee and Datta, Nat. Commun. 10, 2075 (2019).NCAOBW2041-172310.1038/s41467-019-10115-1 and Pseudomonas putida Alirezaeizanjani et al., Sci. Adv. 6, eaaz6153 (2020).SACDAF2375-254810.1126/sciadv.aaz6153, perform distinct modes of motion when placed in porous media as compared to dilute regions or free space. This has led us to suggest an efficient strategy for active particles in a disordered environment: reorientations are suppressed in locally dilute regions and intensified in locally dense ones. Thereby the local geometry determines the optimal path of the active agent and substantially accelerates the dynamics for up to 2 orders of magnitude. We observe a nonmonotonic behavior of the diffusion coefficient in dependence on the tumbling rate and identify a localization transition, either by increasing the density of obstacles or by decreasing the reorientation rate.

Physical mechanisms of chromatin spatial organization.

In higher eukaryotes, chromosomes have a complex three-dimensional (3D) conformation in the cell nucleus serving vital functional purposes, yet their folding principles remain poorly understood at the single-molecule level. Here, we summarize recent approaches from polymer physics to comprehend the physical mechanisms underlying chromatin architecture. In particular, we focus on two models that have been supported by recent, growing experimental evidence, the Loop Extrusion model and the Strings&Binders phase separation model. We discuss their key ingredients, how they compare to experimental data and some insight they provide on chromatin architecture and gene regulation. Progress in that research field are opening the possibility to predict how genomic mutations alter the network of contacts between genes and their regulators and how that is linked to genetic diseases, such as congenital disorders and cancer.

Cell-type specialization is encoded by specific chromatin topologies.

The three-dimensional (3D) structure of chromatin is intrinsically associated with gene regulation and cell function1-3. Methods based on chromatin conformation capture have mapped chromatin structures in neuronal systems such as in vitro differentiated neurons, neurons isolated through fluorescence-activated cell sorting from cortical tissues pooled from different animals and from dissociated whole hippocampi4-6. However, changes in chromatin organization captured by imaging, such as the relocation of Bdnf away from the nuclear periphery after activation7, are invisible with such approaches8. Here we developed immunoGAM, an extension of genome architecture mapping (GAM)2,9, to map 3D chromatin topology genome-wide in specific brain cell types, without tissue disruption, from single animals. GAM is a ligation-free technology that maps genome topology by sequencing the DNA content from thin (about 220 nm) nuclear cryosections. Chromatin interactions are identified from the increased probability of co-segregation of contacting loci across a collection of nuclear slices. ImmunoGAM expands the scope of GAM to enable the selection of specific cell types using low cell numbers (approximately 1,000 cells) within a complex tissue and avoids tissue dissociation2,10. We report cell-type specialized 3D chromatin structures at multiple genomic scales that relate to patterns of gene expression. We discover extensive 'melting' of long genes when they are highly expressed and/or have high chromatin accessibility. The contacts most specific of neuron subtypes contain genes associated with specialized processes, such as addiction and synaptic plasticity, which harbour putative binding sites for neuronal transcription factors within accessible chromatin regions. Moreover, sensory receptor genes are preferentially found in heterochromatic compartments in brain cells, which establish strong contacts across tens of megabases. Our results demonstrate that highly specific chromatin conformations in brain cells are tightly related to gene regulation mechanisms and specialized functions.

Athermal rheology of weakly attractive soft particles.

We study the rheology of a soft particulate system where the interparticle interactions are weakly attractive. Using extensive molecular dynamics simulations, we scan across a wide range of packing fractions (ϕ), attraction strengths (u), and imposed shear rates (γ[over ̇]). In striking contrast to repulsive systems, we find that at small shear rates generically a fragile isostatic solid is formed even if we go to ϕ≪ϕ_{J}. Further, with increasing shear rates, even at these low ϕ, nonmonotonic flow curves occur which lead to the formation of persistent shear bands in large enough systems. By tuning the damping parameter, we also show that inertia plays an important role in this process. Furthermore, we observe enhanced particle dynamics in the attraction-dominated regime as well as a pronounced anisotropy of velocity and diffusion constant, which we take as precursors to the formation of shear bands. At low enough ϕ, we also observe structural changes via the interplay of low shear rates and attraction with the formation of microclusters and voids. Finally, we characterize the properties of the emergent shear bands, and thereby, we find surprisingly small mobility of these bands, leading to prohibitively long time scales and extensive history effects in ramping experiments.

Impact of attractive interactions on the rheology of dense athermal particles.

Using numerical simulations, the rheological response of an athermal assembly of soft particles with tunable attractive interactions is studied in the vicinity of jamming. At small attractions, a fragile solid develops and a finite yield stress is measured. Moreover, the measured flow curves have unstable regimes, which lead to persistent shear banding. These features are rationalized by establishing a link between the rheology and the interparticle connectivity, which also provides a minimal model to describe the flow curves.