Davide Marenduzzo

Localisation of DivIVA by targeting to negatively curved membranes

DivIVA is a conserved protein in Gram‐positive bacteria and involved in various processes related to cell growth, cell division and spore formation. DivIVA is specifically targeted to cell division sites and cell poles. In Bacillus subtilis, DivIVA helps to localise other proteins, such as the conserved cell division inhibitor proteins, MinC/MinD, and the chromosome segregation protein, RacA. Little is known about the mechanism that localises DivIVA. Here we show that DivIVA binds to liposomes, and that the N terminus harbours the membrane targeting sequence. The purified protein can stimulate binding of RacA to membranes. In mutants with aberrant cell shapes, DivIVA accumulates where the cell membrane is most strongly curved. On the basis of electron microscopic studies and other data, we propose that this is due to molecular bridging of the curvature by DivIVA multimers. This model may explain why DivIVA localises at cell division sites. A Monte‐Carlo simulation study showed that molecular bridging can be a general mechanism for binding of proteins to negatively curved membranes.

The depletion attraction: an underappreciated force driving cellular organization

Cellular structures are shaped by hydrogen and ionic bonds, plus van der Waals and hydrophobic forces. In cells crowded with macromolecules, a little-known and distinct force—the “depletion attraction”—also acts. We review evidence that this force assists in the assembly of a wide range of cellular structures, ranging from the cytoskeleton to chromatin loops and whole chromosomes.

Phase separation and rotor self-assembly in active particle suspensions.

Adding a nonadsorbing polymer to passive colloids induces an attraction between the particles via the “depletion” mechanism. High enough polymer concentrations lead to phase separation. We combine experiments, theory, and simulations to demonstrate that using active colloids (such as motile bacteria) dramatically changes the physics of such mixtures. First, significantly stronger interparticle attraction is needed to cause phase separation. Secondly, the finite size aggregates formed at lower interparticle attraction show unidirectional rotation. These micro-rotors demonstrate the self-assembly of functional structures using active particles. The angular speed of the rotating clusters scales approximately as the inverse of their size, which may be understood theoretically by assuming that the torques exerted by the outermost bacteria in a cluster add up randomly. Our simulations suggest that both the suppression of phase separation and the self-assembly of rotors are generic features of aggregating swimmers and should therefore occur in a variety of biological and synthetic active particle systems.

Polymers with spatial or topological constraints: Theoretical and computational results

In this review, we provide an organized summary of the theoretical and computational results that are available for polymers subject to spatial or topological constraints. Because of the interdisciplinary character of the topic, we provide an accessible, non-specialist introduction to the main topological concepts, polymer models, and theoretical/computational methods used to investigate dense and entangled polymer systems. The main body of our review deals with (i) the effect that spatial confinement has on the equilibrium topological entanglement of one or more polymer chains and (ii) the metric and entropic properties of polymer chains with fixed topological states. These problems have important technological applications and implications for life sciences. Both aspects, especially the latter, are amply covered. A number of selected open problems are finally highlighted.

Arrested phase separation in reproducing bacteria creates a generic route to pattern formation

We present a generic mechanism by which reproducing microorganisms, with a diffusivity that depends on the local population density, can form stable patterns. For instance, it is known that a decrease of bacterial motility with density can promote separation into bulk phases of two coexisting densities; this is opposed by the logistic law for birth and death that allows only a single uniform density to be stable. The result of this contest is an arrested nonequilibrium phase separation in which dense droplets or rings become separated by less dense regions, with a characteristic steady-state length scale. Cell division predominates in the dilute regions and cell death in the dense ones, with a continuous flux between these sustained by the diffusivity gradient. We formulate a mathematical model of this in a case involving run-and-tumble bacteria and make connections with a wider class of mechanisms for density-dependent motility. No chemotaxis is assumed in the model, yet it predicts the formation of patterns strikingly similar to some of those believed to result from chemotactic behavior.

DNA–DNA interactions in bacteriophage capsids are responsible for the observed DNA knotting

Recent experiments showed that the linear double-stranded DNA in bacteriophage capsids is both highly knotted and neatly structured. What is the physical basis of this organization? Here we show evidence from stochastic simulation techniques that suggests that a key element is the tendency of contacting DNA strands to order, as in cholesteric liquid crystals. This interaction favors their preferential juxtaposition at a small twist angle, thus promoting an approximately nematic (and apolar) local order. The ordering effect dramatically impacts the geometry and topology of DNA inside phages. Accounting for this local potential allows us to reproduce the main experimental data on DNA organization in phages, including the cryo-EM observations and detailed features of the spectrum of DNA knots formed inside viral capsids. The DNA knots we observe are strongly delocalized and, intriguingly, this is shown not to interfere with genome ejection out of the phage.

Entropic organization of interphase chromosomes

Nonspecific forces, in addition to biophysical properties, lead to the careful arrangement of chromosomes in the nucleus.

Continuum Theory of Phase Separation Kinetics for Active Brownian Particles

Active Brownian particles (ABPs), when subject to purely repulsive interactions, are known to undergo activity-induced phase separation broadly resembling an equilibrium (attraction-induced) gas-liquid coexistence. Here we present an accurate continuum theory for the dynamics of phase-separating ABPs, derived by direct coarse graining, capturing leading-order density gradient terms alongside an effective bulk free energy. Such gradient terms do not obey detailed balance; yet we find coarsening dynamics closely resembling that of equilibrium phase separation. Our continuum theory is numerically compared to large-scale direct simulations of ABPs and accurately accounts for domain growth kinetics, domain topologies, and coexistence densities.

Pattern formation in self-propelled particles with density-dependent motility.

We study the behavior of interacting self-propelled particles, whose self-propulsion speed decreases with their local density. By combining direct simulations of the microscopic model with an analysis of the hydrodynamic equations obtained by explicitly coarse graining the model, we show that interactions lead generically to the formation of a host of patterns, including moving clumps, active lanes, and asters. This general mechanism could explain many of the patterns seen in recent experiments and simulations.

Structure of Blue Phase III of Cholesteric Liquid Crystals

We report large scale simulations of the blue phases of cholesteric liquid crystals. Our results suggest a structure for blue phase III, the blue fog, which has been the subject of a long debate in liquid crystal physics. We propose that blue phase III is an amorphous network of disclination lines, which is thermodynamically and kinetically stabilised over crystalline blue phases at intermediate chiralities. This amorphous network becomes ordered under an applied electric field, as seen in experiments.