Dominating lengthscales of zebrafish collective behaviour

Collective behaviour in living systems is observed across many scales, from bacteria to insects, to fish shoals. Zebrafish have emerged as a model system amenable to laboratory study. Here we report a three-dimensional study of the collective dynamics of fifty zebrafish. We observed the emergence of collective behaviour changing between ordered to randomised, upon adaptation to new environmental conditions. We quantify the spatial and temporal correlation functions of the fish and identify two length scales, the persistence length and the nearest neighbour distance, that capture the essence of the behavioural changes. The ratio of the two length scales correlates robustly with the polarisation of collective motion that we explain with a reductionist model of self–propelled particles with alignment interactions.

Hydrodynamic and Polyelectrolyte Properties of Actin Filaments: Theory and Experiments

Actin filament′s polyelectrolyte and hydrodynamic properties, their interactions with the biological environment, and external force fields play an essential role in their biological activities in eukaryotic cellular processes. In this article, we introduce a unique approach that combines dynamics and electrophoresis light scattering experiments, an extended semiflexible worm-like chain model, and an asymmetric polymer length distribution theory to characterize the polyelectrolyte and hydrodynamic properties of actin filaments in aqueous electrolyte solutions. We used the same sample and experimental conditions and considered several g-actin and polymerization buffers to elucidate the impact of their chemical composition, reducing agents, pH values, and ionic strengths on the filament translational diffusion coefficient, electrophoretic mobility, structure factor, asymmetric length distribution, effective filament diameter, electric charge, zeta potential, and semiflexibility. Compared to those values obtained from molecular structure models, our results revealed a lower value of the effective G-actin charge and a more significant value of the effective filament diameter due to the formation of the double layer of the electrolyte surrounding the filaments. Additionally, compared to the values usually reported from electron micrographs, the lower values of our results for the persistence length and average contour filament length agrees with the significant difference in the association rates at the filament ends that shift to submicro lengths, the maximum of the length distribution.

Cross-Scale Synthesis of Organic High-k Semiconductors Based on Spiro-Gridized Nanopolymers

High dielectric constants in organic semiconductors have been identified as a central challenge for the improvement in not only piezoelectric, pyroelectric, and ferroelectric effects but also photoelectric conversion efficiency in OPVs, carrier mobility in OFETs, and charge density in charge-trapping memories. Herein, we report an ultralong persistence length (lp≈41 nm) effect of spiro-fused organic nanopolymers on dielectric properties, together with excitonic and charge carrier behaviors. The state-of-the-art nanopolymers, namely, nanopolyspirogrids (NPSGs), are synthesized via the simple cross-scale Friedel-Crafts polygridization of A2B2-type nanomonomers. The high dielectric constant (k=8.43) of NPSG is firstly achieved by locking spiro-polygridization effect that results in the enhancement of dipole polarization. When doping into a polystyrene-based dielectric layer, such a high-k feature of NPSG increases the field-effect carrier mobility from 0.20 to 0.90 cm2 V-1 s-1 in pentacene OFET devices. Meanwhile, amorphous NPSG film exhibits an ultralow energy disorder (<50 meV) for an excellent zero-field hole mobility of 3.94×10−3 cm2 V−1 s−1, surpassing most of the amorphous π-conjugated polymers. Organic nanopolymers with high dielectric constants open a new way to break through the bottleneck of efficiency and multifunctionality in the blueprint of the fourth-generation semiconductors.

Effective elasticity and persistence of strain in active filament-motor assemblies

Cross-linked, elastic, filamentous networks that are deformed by active molecular motors feature in several natural and synthetic settings. The effective active elasticity of these composite systems determines the length scale over which active deformations persist in fluctuating environments. This fundamental quantity has been studied in passive systems; however mechanisms determining and modulating this length-scale in active systems has not been clarified. Here, focusing on active arrayed filament-motor assemblies, we propose and analyze a minimal model in order to estimate the length scale over which imposed or emergent elastic deformations or stresses persist. We combine a mean-field continuum theory valid for weakly elastic assemblies with high dimensional Multi-Particle Collision (MPC) based Brownian simulations valid for moderate to strongly elastic and noisy systems. Integrating analytical and numerical results, we show that localized strains - steady or oscillatory - persist over well-defined length scales that dependent on motor activity, effective shear elasticity and filament extensibility. Extensibility is key even in very stiff filaments, and cannot be ignored when global deformations are considered. We clarify mechanisms by which motor derived active elasticity and passive shear elasticity of the filamentous backbone combine to effectively soften filaments. Surprisingly, the predictions of the mean-field theory agree qualitatively with results from stochastic discrete filament-motor model, even for moderately strong noise. We also find that athermal motor noise impacts the overall duty ratio of the motors and thereby the persistence length in these driven assemblies. Our study demonstrates how correlated activity in natural ordered active matter possesses a finite range of influence with clear testable experimental implications.

Experimental Measurement of Sharp THz Absorption Signatures from Nucleic Acid Solutions in Nanofluidic Channels

We report on the room-temperature experimental measurement of THz absorption signatures in aqueous, double-stranded nucleic acid solutions confined to the submicron silica channels on fused quartz substrates using THz frequency-domain (photomixing) spectroscopy. Three sharp (i.e., strong and narrow) signatures, ~10–20 GHz FWHM, are observed in the shortest base pair sample—small interfering, double-stranded (ds) RNA—in the range of 800 GHz to 1.1 THz. Three similar signatures are also observed in a 50-bp dsDNA ladder sample. For a 1-kbp dsDNA ladder sample, the three are still evident, but are broadened and weakened. For a 48.5-kbp sample (λ-DNA), no prominent signatures are observed, but rather a quasi-sinusoidal transmittance spectrum consistent with a substrate etalon effect. The division between sharp signatures and no signatures is consistent with the molecular length being shorter or longer than the persistence length.

Molecular mechanism of claudin-15 strand flexibility

Claudins are one of the major components of tight junctions that play a key role in formation and maintaining epithelial barrier function. Tight junction strands are dynamic and capable of adapting their structure in response to large-scale tissue rearrangement and cellular movement. Here, we present molecular dynamics simulations of claudin-15 strands of up to 225 nm in length in two parallel lipid membranes and characterize their mechanical properties. The persistence length of claudin-15 strands is comparable with experiments leading to a curvature of 0.12 nm−1 at room temperature. Our results indicate that lateral flexibility of claudin strands is due to an interplay of three sets of interfacial interaction networks between four linear claudin strands in the membranes. In this model, claudins are assembled into interlocking tetrameric ion channels along the strand that slide with respect to each other as the strands curve over sub-micrometer length scales. These results suggest a novel molecular mechanism underlying claudin-15 strand flexibility. It also sheds light on the inter-molecular interactions and their role in maintaining epithelial barrier function.

Accurate sequence-dependent coarse-grained model for conformational and elastic properties of double-stranded DNA

We introduce MADna, a sequence-dependent coarse-grained model of double-stranded DNA (dsDNA), where each nucleotide is described by three beads localized at the sugar and base moieties, and at the phosphate group. The sequence dependence is included by considering a step-dependent parameterization of the bonded interactions, which are tuned in order to reproduce the values of key observables obtained from exhaustive atomistic simulations from literature. The predictions of the model are benchmarked against an independent set of all-atom simulations, showing that it captures with high fidelity the sequence dependence of conformational and elastic features beyond the single step considered in its formulation. A remarkably good agreement with experiments is found for both sequence-averaged and sequence-dependent conformational and elastic features, including the stretching and torsion moduli, the twist-stretch and twist-bend couplings, the persistence length and the helical pitch. Overall, for the inspected quantities, the model has a precision comparable to atomistic simulations, hence providing a reliable coarse-grained description for the rationalization of singlemolecule experiments and the study of cellular processes involving dsDNA. Owing to the simplicity of its formulation, MADna can be straightforwardly included in common simulation engines.

Morphological fluctuations of individual mitochondria in living cells

Uncovering the link between mitochondrial morphology, dynamics, positioning and function is challenging. Mitochondria are very flexible organelles that are subject to tension and compression within cells. Recent findings highlighted the importance of these mechanical aspects in the regulation of mitochondria dynamics, arising the question on which are the processes and mechanisms involved in their shape remodeling. In this work we explored in detail the morphological changes and spatio- temporal fluctuations of these organelles in living Xenopus laevis melanophores, a well- characterized cellular model. We developed an automatic method for the classification of mitochondria shapes based on the analysis of the curvature of the contour shape from confocal microscopy images. A persistence length of 2.1 μm was measured, quantifying, for the first time, the bending plasticity of mitochondria in their cellular environment. The shape evolution at the single organelle level was followed during a few minutes revealing that mitochondria can bend and unbend in the seconds timescale. Furthermore, the inspection of confocal movies simultaneously registering fluorescent mitochondria and microtubules suggests that the cytoskeleton network architecture and dynamics play a significant role in mitochondria shape remodeling and fluctuations. For instance changes from sinuous to elongated organelles related to transitions from confined behavior to fast directed motion along microtubule tracks were observed.

A deep learning framework for quantitative analysis of actin microridges

Microridges are evolutionarily conserved actin-rich protrusions present on the apical surface of the squamous epithelial cells. In zebrafish epidermal cells, microridges form self-evolving patterns due to the underlying actomyosin network dynamics. However, their morphological and dynamic characteristics have remained poorly understood owing to lack of automated segmentation methods. We achieved ~97% pixel-level accuracy with the deep learning microridge segmentation strategy enabling quantitative insights into their bio-physical-mechanical characteristics. From the segmented images, we estimated an effective microridge persistence length as ~0.61μm. We discovered the presence of mechanical fluctuations and found relatively greater stresses stored within patterns of yolk than flank, indicating distinct regulation of their actomyosin networks. Furthermore, spontaneous formations and positional fluctuations of actin clusters within microridge influenced pattern rearrangements over short length/time-scales. Our framework allows large-scale spatiotemporal analysis of microridges during epithelial development and probing of their responses to chemical and genetic perturbations to unravel the underlying patterning mechanisms.

A theory of the dynamics of DNA loop initiation in condensin/cohesin complexes

The structural maintenance of chromosome complexes exhibit the remarkable ability to actively extrude DNA, which has led to the appealing and popular "loop extrusion" model to explain one of the most important processes in biology: the compaction of chromatin during the cell cycle. A potential mechanism for the action of extrusion is the classic Brownian ratchet, which requires short DNA loops to overcome an initial enthalpic barrier to bending, before favoured entropic growth of longer loops. We present a simple model of the constrained dynamics of DNA loop formation based on a frictional worm like chain, where for circular loops of order, or smaller than the persistence length, internal friction to bending dominates solvent dynamics. Using Rayleigh's dissipation function, we show how bending friction can be translated to simple one dimensional diffusion of the angle of the loop resulting in a Smoluchowski equation with a coordinate dependent diffusion constant. This interplay between Brownian motion, bending dissipation and geometry of loops leads to a qualitatively new phenomenon, where the friction vanishes for bends with an angle of exactly 180°, due to a decoupling between changes in loop curvature and angle. Using this theory and given current parameter uncertainties, we tentatively predict mean first passage times of between 1 and 10 seconds, which is of order the cycle time of ATP, suggesting spontaneous looping could be sufficient to achieve efficient initiation of looping.