Bacterial cell-size changes resulting from altering the relative expression of Min proteins.

The timing of cell division, and thus cell size in bacteria, is determined in part by the accumulation dynamics of the protein FtsZ, which forms the septal ring. FtsZ localization depends on membrane-associated Min proteins, which inhibit FtsZ binding to the cell pole membrane. Changes in the relative concentrations of Min proteins can disrupt FtsZ binding to the membrane, which in turn can delay cell division until a certain cell size is reached, in which the dynamics of Min proteins frees the cell membrane long enough to allow FtsZ ring formation. Here, we study the effect of Min proteins relative expression on the dynamics of FtsZ ring formation and cell size in individual Escherichia coli bacteria. Upon inducing overexpression of minE, cell size increases gradually to a new steady-state value. Concurrently, the time required to initiate FtsZ ring formation grows as the size approaches the new steady-state, at which point the ring formation initiates as early as before induction. These results highlight the contribution of Min proteins to cell size control, which may be partially responsible for the size fluctuations observed in bacterial populations, and may clarify how the size difference acquired during asymmetric cell division is offset.

Shape transitions in a network model of active elastic shells.

Morphogenesis involves the transformation of initially simple shapes, such as multicellular spheroids, into more complex 3D shapes. These shape changes are governed by mechanical forces including molecular motor-generated forces as well as hydrostatic fluid pressure, both of which are actively regulated in living matter through mechano-chemical feedback. Inspired by autonomous, biophysical shape change, such as occurring in the model organism hydra, we introduce a minimal, active, elastic model featuring a network of springs in a globe-like spherical shell geometry. In this model there is coupling between activity and the shape of the shell: if the local curvature of a filament represented by a spring falls below a critical value, its elastic constant is actively changed. This results in deformation of the springs that changes the shape of the shell. By combining excitation of springs and pressure regulation, we show that the shell undergoes a transition from spheroidal to either elongated ellipsoidal or a different spheroidal shape, depending on pressure. There exists a critical pressure at which there is an abrupt change from ellipsoids to spheroids, showing that pressure is potentially a sensitive switch for material shape. We thus offer biologically inspired design principles for autonomous shape transitions in active elastic shells.

Network model of active elastic shells swollen by hydrostatic pressure.

Many organisms have an elastic skeleton that consists of a closed shell of epithelial cells that is filled with fluid, and can actively regulate both elastic forces in the shell and hydrostatic pressure inside it. In this work we introduce a simple network model of such pressure-stabilized active elastic shells in which cross-links are represented by material points connected by non-linear springs of some given equilibrium lengths and spring constants. We mimic active contractile forces in the system by changing the parameters of randomly chosen springs and use computer simulations to study the resulting local and global deformation dynamics of the network. We elucidate the statistical properties of these deformations by computing the corresponding distributions and correlation functions. We show that pressure-induced stretching of the network introduces coupling between its local and global behavior: while the network opposes the contraction of each excited spring and affects the amplitude and relaxation time of its deformation, random local excitations give rise to contraction of the network and to fluctuations of its surface area.

Reentrant transitions in a mixture of small and big particles interacting via soft repulsive potential.

We report an observation of a temperature-controlled reentrant transition in simulations of mixtures of small and big particles interacting via a soft repulsive potential in two dimensions. As temperature increases, the system passes from a fluid mixture, to a crystal of big particles in a fluid of small particles, and back to a fluid mixture. Solidification is driven by entropy gain of small particles which overcomes the free-energy cost of confining big ones. Melting results from enhanced interpenetration of particles at high temperature which reduces the entropic forces that stabilize the crystal.

Anomalous Temperature-Controlled Concave-Convex Switching of Curved Oil-Water Menisci.

While the curvature of the classical liquid surfaces exhibits only a weak temperature dependence, we demonstrate here a reversible temperature-tunable concave-convex shape switching in capillary-contained, surfactant-decorated, oil-water interfaces. The observed switching gives rise to a concave-convex shape transition, which takes place as a function of the width of the containing capillary. This apparent violation of Young's equation results from a hitherto-unreported sharp reversible hydrophobic-hydrophilic transition of the glass capillary walls. The transition is driven by the interfacial freezing effect, which controls the balance between the competing surfactants' adsorption on, and consequent hydrophobization of, the capillary walls and their incorporation into the interfacially frozen monolayer. Since capillary wetting by surfactant solutions is fundamental for a wide range of technologies and natural phenomena, the present observations have important implications in many fields, from fluid engineering to biology, and beyond.

Sequence effects on internal structure of droplets of associative polymers.

Intrinsically disordered proteins (IDPs) can form liquid-like membraneless organelles, gels, and fibers in cells and in vitro. In this study, we propose a simple model of IDPs as associative polymers in poor solvent and explore the formation of transient liquid droplets and their transformation into solid-like aggregates. We use Langevin dynamics simulations of short polymers with two stickers placed symmetrically along their contour to study the effect of the primary sequence of these polymers on their organization inside condensed droplets. We observe that the shape, size, and number of sticker clusters inside the droplet change from a long cylindrical fiber to many compact clusters as one varies the location of stickers along the chain contour. Aging caused by the conversion of intramoleclular to intermolecular associations is observed in droplets of telechelic polymers but not for other sequences of associating polymers. The relevance of our results to condensates of IDPs is discussed.

Systems with Size and Energy Polydispersity: From Glasses to Mosaic Crystals.

We use Langevin dynamics simulations to study dense 2d systems of particles with both size and energy polydispersity. We compare two types of bidisperse systems which differ in the correlation between particle size and interaction parameters: in one system big particles have high interaction parameters and small particles have low interaction parameters, while in the other system the situation is reversed. We study the different phases of the two systems and compare them to those of a system with size but not energy bidispersity. We show that, depending on the strength of interaction between big and small particles, cooling to low temperatures yields either homogeneous glasses or mosaic crystals. We find that systems with low mixing interaction, undergo partial freezing of one of the components at intermediate temperatures, and that while this phenomenon is energy-driven in both size and energy bidisperse systems, it is controlled by entropic effects in systems with size bidispersity only.

Non-equilibrium interaction between catalytic colloids: boundary conditions and penetration depth.

Spherical colloids that catalyze the interconversion reaction A⇋B between solute molecules A and B whose concentration at infinity is maintained away from equilibrium effectively interact due to the non-uniform fields of solute concentrations. We show that this long range 1/r interaction is suppressed via a mechanism that is superficially reminiscent but qualitatively very different from electrostatic screening: catalytic activity drives the concentrations of solute molecules towards their equilibrium values and reduces the chemical imbalance that drives the interaction between the colloids. The imposed non-equilibrium boundary conditions give rise to a variety of geometry-dependent scenarios; while long-range interactions are suppressed (except for a finite penetration depth) in the bulk of the colloid solution in 3D, they can persist in quasi-2D geometry in which the colloids but not the solutes are confined to a surface, resulting in the formation of clusters or Wigner crystals, depending on the sign of the interaction between colloids.

Nanocompartmentalization of the Nuclear Pore Lumen.

The nuclear pore complex (NPC) employs the intrinsically disordered regions (IDRs) from a family of phenylalanine-glycine-rich nucleoporins (FG-Nups) to control nucleocytoplasmic transport. It has been a long-standing mystery how the IDR-mediated mass exchange can be rapid yet selective. Here, we use a computational microscope to show that nanocompartmentalization of IDR subdomains leads to a remarkably elaborate gating structure as programmed by the amino acid sequences. In particular, we reveal a heterogeneous permeability barrier that combines an inner ring barrier with two vestibular condensates. Throughout the NPC, we find a polarized electrostatic potential and a diffuse thermoreversible FG network featuring mosaic FG territories with low FG-FG pairing fraction. Our theoretical anatomy of the central transporter sheds light into the sequence-structure-function relationship of the FG-Nups and provides a picture of nucleocytoplasmic mass exchange that allows a reconciliation of transport efficiency and specificity.

Assembly along lines in boundary-driven dynamical system.

We introduce a simple dynamical rule in which each particle locates a particle that is farthest from it and moves towards it. Repeated application of this algorithm results in the formation of unusual dynamical patterns: during the process of assembly the system self-organizes into slices of low particle density separated by lines of increasingly high particle density along which most particles move. As the process proceeds, pairs of lines meet and merge with each other until a single line remains and particles move along it towards the zone of assembly. We show that this pattern is governed by particles (attractors) situated on the instantaneous outer boundary of the system and that both in two and in three dimensions the lines are formed by zigzag motion of a particle towards a pair of nearly equidistant attractors. This novel line-dominated assembly is very different from the local assembly in which particles that move towards their nearest neighbors produce point-like clusters that coalesce into new point-like clusters, etc.

Effect of Liquid State Organization on Nanostructure and Strength of Model Multicomponent Solids.

When a multicomponent liquid composed of particles with random interactions is slowly cooled below the freezing temperature, the fluid reorganizes in order to increase (decrease) the number of strong (weak) attractive interactions and solidifies into a structure composed of domains of strongly and of weakly interacting particles. Using Langevin dynamics simulations of a model system we find that the tensile strength, mode of fracture, and thermal stability of such solids differ from those of one-component solids and that these properties can be controlled by the method of preparation.

Chemically active nanodroplets in a multi-component fluid.

We introduce a model of chemically active particles of a multi-component fluid that can change their interactions with other particles depending on their state. Since such switching of interactions can only be maintained by the input of chemical energy, the system is inherently non-equilibrium. Focusing on a scenario where the equilibrium interactions would lead to condensation into a liquid droplet, and despite the relative simplicity of the interaction rules, these systems display a wealth of interesting and novel behaviors such as oscillations of droplet size and molecular sorting, and raise the possibility of spatio-temporal control of chemical reactions on the nanoscale.

Oxidised low-density lipoprotein, a possible distinguishing lipid profile biomolecule between prostate cancer and benign prostatic hyperplasia.

Benign prostatic hyperplasia (BPH) and prostate cancer (PCa) share common conditions such as lower urinary tract symptoms (LUTS) and dyslipidaemia. Whether an extensive lipid profile analysis could discriminate between BPH and PCa was the objective. Thirty-six (36) BPH and twenty (20) PCa outpatients of a urology clinic plus forty (40) controls without LUTS, but normal PSA, were recruited. Body mass index (BMI), lipid profile (total cholesterol [CHOL], triglycerides [TG], high-density lipoprotein [HDL], very-low-density lipoprotein [VLDL], low-density lipoprotein [LDL] and Castelli's risk index I [CR I] [TC/HDL]), oxidised LDL, apolipoprotein E, ceramide and PSA were determined. Mean ages for BPH, PCa and control were 69 ± 13, 67 ± 10 and 53 ± 7 years respectively. Most parameters apart from BMI and HDL were significantly different compared to the control group. oxLDL for BPH versus control, PCa versus control and BPH versus PCa was significant (p < 0.001, p = 0.02 and p < 0.001 respectively). Ceramide showed significant group differences. Between BPH and PCa, total cholesterol, LDL and Apo E were significantly different (p = 0.00, p = 0.01 and p = 0.03 respectively). Apo E could potentially be a discriminating biomarker. Receiver operating characteristic curves for TPSA, Apo E and oxLDL demonstrated sensitivity of 69.44 and specificity of 88.24 for oxLDL, hence more discriminatory.

Identity ordering and metastable clusters in fluids with random interactions.

We use Langevin dynamics simulations to study dense two-dimensional systems of particles where all binary interactions are different in the sense that each interaction parameter is characterized by a randomly chosen number. We compare two systems that differ by the probability distributions from which the interaction parameters are drawn: uniform (U) and exponential (E). Both systems undergo neighborhood identity ordering and form metastable clusters in the fluid phase near the liquid-solid transition, but the effects are much stronger in E than in U systems. Possible implications of our results for the control of the structure of multicomponent alloys are discussed.

Composition, morphology, and growth of clusters in a gas of particles with random interactions.

We use Langevin dynamics simulations to study the growth kinetics and the steady-state properties of condensed clusters in a dilute two-dimensional system of particles that are all different (APD) in the sense that each particle is characterized by a randomly chosen interaction parameter. The growth exponents, the transition temperatures, and the steady-state properties of the clusters and of the surrounding gas phase are obtained and compared with those of one-component systems. We investigate the fractionation phenomenon, i.e., how particles of different identities are distributed between the coexisting mother (gas) and daughter (clusters) phases. We study the local organization of particles inside clusters, according to their identity-neighbourhood identity ordering (NIO)-and compare the results with those of previous studies of NIO in dense APD systems.

Effect of Grafting on Aggregation of Intrinsically Disordered Proteins.

A significant part of the proteome is composed of intrinsically disordered proteins (IDPs). These proteins do not fold into a well-defined structure and behave like ordinary polymers. In this work, we consider IDPs that have the tendency to aggregate, model them as heteropolymers that contain a small number of associating monomers, and use computer simulations to compare the aggregation of such IDPs that are grafted to a surface or free in solution. We then discuss how such grafting may affect the analysis of in vitro experiments and could also be used to suppress harmful aggregation.

Darwinian selection of host and bacteria supports emergence of Lamarckian-like adaptation of the system as a whole.

BACKGROUND: The relatively fast selection of symbiotic bacteria within hosts and the potential transmission of these bacteria across generations of hosts raise the question of whether interactions between host and bacteria support emergent adaptive capabilities beyond those of germ-free hosts. RESULTS: To investigate possibilities for emergent adaptations that may distinguish composite host-microbiome systems from germ-free hosts, we introduce a population genetics model of a host-microbiome system with vertical transmission of bacteria. The host and its bacteria are jointly exposed to a toxic agent, creating a toxic stress that can be alleviated by selection of resistant individuals and by secretion of a detoxification agent ("detox"). We show that toxic exposure in one generation of hosts leads to selection of resistant bacteria, which in turn, increases the toxic tolerance of the host's offspring. Prolonged exposure to toxin over many host generations promotes anadditional form of emergent adaptation due to selection of hosts based on detox produced by their bacterial community as a whole (as opposed to properties of individual bacteria). CONCLUSIONS: These findings show that interactions between pure Darwinian selections of host and its bacteria can give rise to emergent adaptive capabilities, including Lamarckian-like adaptation of the host-microbiome system. REVIEWERS: This article was reviewed by Eugene Koonin, Yuri Wolf and Philippe Huneman.

Dynamics of active Rouse chains.

We consider how active forces modeled as non-thermal random noise affect the average dynamical properties of a Rouse polymer. As the power spectrum of the noise is not known we keep the analytical treatment as generic as possible and then present results for a few examples of active noise. We discuss the connection between our results and recent experimental studies of dynamics of labeled DNA telomeres in living cells, and propose new chromatin tracking experiments that will allow one to determine the statistical properties of the active forces associated with chromatin remodeling processes.

Direct observation of DNA knots using a solid-state nanopore.

Long DNA molecules can self-entangle into knots. Experimental techniques for observing such DNA knots (primarily gel electrophoresis) are limited to bulk methods and circular molecules below 10 kilobase pairs in length. Here, we show that solid-state nanopores can be used to directly observe individual knots in both linear and circular single DNA molecules of arbitrary length. The DNA knots are observed as short spikes in the nanopore current traces of the traversing DNA molecules and their detection is dependent on a sufficiently high measurement resolution, which can be achieved using high-concentration LiCl buffers. We study the percentage of molecules with knots for DNA molecules of up to 166 kilobase pairs in length and find that the knotting occurrence rises with the length of the DNA molecule, consistent with a constant knotting probability per unit length. Our experimental data compare favourably with previous simulation-based predictions for long polymers. From the translocation time of the knot through the nanopore, we estimate that the majority of the DNA knots are tight, with remarkably small sizes below 100 nm. In the case of linear molecules, we also observe that knots are able to slide out on application of high driving forces (voltage).

Effect of non-specific interactions on formation and stability of specific complexes.

We introduce a simple model to describe the interplay between specific and non-specific interactions. We study the influence of various physical factors on the static and dynamic properties of the specific interactions of our model and show that contrary to intuitive expectations, non-specific interactions can assist in the formation of specific complexes and increase their stability. We then discuss the relevance of these results for biological systems.