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Filamentous actin, a species of dynamic protein polymers, is one of the main components of the cytoskeleton of eukaryotic cells. We formulate a class of models that predict the possibility of bistable steady states in populations of dynamic actin filaments. They are built upon a basic model of actin dynamics that includes severing and capping in the presence of a finite actin monomer pool. The key additional ingredient is the presence of a single species of effector molecules that is partially sequestered to an inactive state by binding to free G-actin. In its unbound active state, this effector species can \emph{enhance} the rate of nucleation of filamentous actin or its growth speed, or \emph{inhibit} the activity of capping or severing proteins. Using an explicit analytical solution of the basic actin dynamics model, we show that bistability is predicted to occur in all of the proposed models. We verify these predictions using particle-based stochastic simulations. In addition, we show that switching between the two stable states can be achieved by transient manipulation of the free G-actin pool size.

We present a systematic study of the influence of cell geometry on the orientational distribution of microtubules (MTs) nucleated from a single microtubule organizing center (MTOC). For simplicity we consider an elliptical cell geometry, a setting appropriate to a generic non-spherical animal cell. Within this context we introduce four models of increasing complexity, in each case introducing additional mechanisms that govern the interaction of the MTs with the cell boundary. In order, we consider the cases: MTs that can bind to the boundary with a fixed mean residence time (M0), force-producing MTs that can slide on the boundary towards the cell poles (MS), MTs that interact with a generic polarity factor that is transported and deposited at the boundary, and which in turn stabilizes the MTs at the boundary (MP), and a final model in which both sliding and stabilization by polarity factors is taken into account (MSP). In the baseline model (M0), the exponential length distribution of MTs causes most of the interactions at the cell boundary to occur along the shorter transverse direction in the cell, leading to transverse biaxial order. MT sliding (MS) is able to reorient the main axis of this biaxial order along the longitudinal axis. The polarization mechanism introduced in MP and MSP overrules the geometric bias towards bipolar order observed in M0 and MS, and allows the establishment of unipolar order either along the short- (MP) or the long cell axis (MSP). The behavior of the latter two models can be qualitatively reproduced by a very simple toy model with discrete MT orientations., Comment: 38 pages, 13 figures

We revisit the field-free Ising model on a square lattice with up to third-neighbour (nnnn) interactions, also known as the $J_{1}$--$J_{2}$--$J_{3}$ model, in the mean-field approximation. Using a systematic enumeration procedure, we show that the region of phase space in which the high-temperature disordered phase is stable against all modes representing periodic magnetisation patterns up to a given size is a convex polytope that can be obtained by solving a standard vertex enumeration problem. Each face of this polytope corresponds to a set of coupling constants for which a single set of modes, equivalent up to a symmetry of the lattice, bifurcates from the disordered solution. While the structure of this polytope is simple in the halfspace $J_{3}>0$, where the nnnn-interaction is ferromagnetic, it becomes increasingly complex in the halfspace $J_{3}<0$, where the antiferromagnetic nnnn-interaction induces strong frustration. We characterize a few salient properties of these `disorder polytopes' in terms of the geometry of the space of contributing modes. We then consider the limit $N\rightarrow\infty$ giving a closed form description of the order-disorder surface in the thermodynamic limit, which shows that for $J_3 <0$ the emergent ordered phases will have a `devil's surface'-like mode structure. Finally, using Monte Carlo simulations, we show that for small periodic systems the mean-field analysis correctly predicts the dominant modes of the ordered phases that develop for coupling constants associated with the centroid of the faces of the disorder polytope.

The interaction between actin filaments and microtubules is crucial for many eukaryotic cellular processes, such as, among others, cell polarization, cell motility and cellular wound healing. The importance of this interaction has long been recognised, yet very little is understood about both the underlying mechanisms and the consequences for the spatial (re)organization of the cellular cytoskeleton. At the same time, understanding the causes and the consequences of the interaction between different biomolecular components are key questions for \emph{in vitro} research involving reconstituted biomolecular systems, especially in the light of current interest in creating minimal synthetic cells. In this light, recent \emph{in vitro} experiments have shown that the actin-microtubule interaction mediated by the cytolinker TipAct, which binds to actin lattice and microtubule tip, causes the directed transport of actin filaments. We develop an analytical theory of dynamically unstable microtubules, nucleated from the center of a spherical cell, in interaction with actin filaments. We show that, depending on the balance between the diffusion of unbound actin filaments and propensity to bind microtubules, actin is either concentrated in the center of the cell, where the density of microtubules is highest, or becomes localized to the cell cortex.

Inspired by recent experiments on the effects of cytosolic crowders on the organization of bacterial chromosomes, we consider a "feather-boa" type model chromosome in the presence of non-additive crowders, encapsulated within a cylindrical cell. We observe spontaneous emergence of complementary helicity of the confined polymer and crowders. This feature is reproduced within a simplified effective model of the chromosome. This latter model further establishes the occurrence of longitudinal and transverse spatial segregation transitions between the chromosome and crowders upon increasing crowder size., Comment: 7 pages, 5 figures; minor modifications; version accepted for publication in Europhysics Letters

Soft living tissues like cartilage can be considered as biphasic materials comprised of a fibrous complex biopolymer network and a viscous background liquid. Here, we show by a combination of experiment and theoretical analysis that both the hydraulic permeability and the elastic properties of (bio)polymer networks can be determined with simple ramp compression experiments in a commercial rheometer. In our approximate closed-form solution of the poroelastic equations of motion, we find the normal force response during compression as a combination of network stress and fluid pressure. Choosing fibrin as a biopolymer model system with controllable pore size, measurements of the full time-dependent normal force during compression are found to be in excellent agreement with the theoretical calculations. The inferred elastic response of large-pore ($\mathrm{\mu m}$) fibrin networks depends on the strain rate, suggesting a strong interplay between network elasticity and fluid flow. Phenomenologically extending the calculated normal force into the regime of nonlinear elasticity, we find strain-stiffening of small-pore (sub-$\mathrm{\mu m}$) fibrin networks to occur at an onset average tangential stress at the gel-plate interface that depends on the polymer concentration in a power-law fashion. The inferred permeability of small-pore fibrin networks scales approximately inverse squared with the fibrin concentration, implying with a microscopic cubic lattice model that the thickness of the fibrin fibers decreases with protein concentration. Our theoretical model provides a new method to obtain the hydraulic permeability and the elastic properties of biopolymer networks and hydrogels with simple compression experiments, and paves the way to study the relation between fluid flow and elasticity in biopolymer networks during dynamical compression.

The cortical microtubule array of dark-grown hypocotyl cells of plant seedlings undergoes a striking, and developmentally significant, reorientation upon exposure to light. This process is driven by the exponential amplification of a population of longitudinal microtubules, created by severing events localized at crossovers with the microtubules of the pre-existing transverse array. We present a dynamic one-dimensional model for microtubule amplification through this type of templated severing. We focus on the role of the probability of immediate rescue-after-severing of the newly-created lagging microtubule, observed to be a characteristic feature of the reorientation process. Employing stochastic simulations, we show that in the dynamic regime of unbounded microtubule growth, a finite value of this probability is not required for amplification to occur, but does strongly influence the degree of amplification, and hence the speed of the reorientation process. In contrast, in the regime of bounded microtubule growth, we show that amplification only occurs above a critical threshold. We construct an approximate analytical theory, based on a priori limiting the number of crossover events considered, which allows us to predict the observed critical value of the rescue-after-severing probability with reasonable accuracy.

Motivated by recent experiments probing shape, size and dynamics of bacterial chromosomes in growing cells, we consider a polymer model consisting of a circular backbone to which side-loops are attached, confined to a cylindrical cell. Such a model chromosome spontaneously adopts a helical shape, which is further compacted by molecular crowders to occupy a nucleoid-like subvolume of the cell. With increasing cell length, the longitudinal size of the chromosome increases in a non-linear fashion to finally saturate, its morphology gradually opening up while displaying a changing number of helical turns. For shorter cells, the chromosome extension varies non-monotonically with cell size, which we show is associated with a radial to longitudinal spatial reordering of the crowders. Confinement and crowders constrain chain dynamics leading to anomalous diffusion. While the scaling exponent for the mean squared displacement of center of mass grows and saturates with cell length, that of individual loci displays broad distribution with a sharp maximum., Comment: 12 pages, 12 figures

These lectures focus on bifurcation analysis as a tool for studying phase transitions that occur in models of liquid-crystalline systems. We show how this approach bridges the gap between the phenomenological Landau theory and the --- often intractable --- full statistical mechanical treatment. Employing a `toy model' as a tutorial example the various ingredients of the technique are presented. Special attention is paid to the way in which one obtains information on the relation between the characteristics of the assumed interparticle interactions (shape, symmetry ...) and global properties of the phase transitions (order, symmetry of resultant phases ...). Finally, a few more involved examples are discussed indicating how the approach can be applied to more realistic models and how it can serve as a complement to simulations., Comment: Unpublished lecture notes originally intended to be published in a volume of proceedings of the NATO Advanced Research Workshop Computer Simulation of Liquid Crystals held at Il Ciocco, Italy between 15-21 sept 1991

The evolution of gene regulatory networks in variable environments poses Multi-objective Optimization Problem (MOP), where the expression levels of genes must be tuned to meet the demands of each environment. When formalized in the context of monotone systems, this problem falls into a sub-class of linear MOPs. Here, the constraints are partial orders and the objectives consist of either the minimization or maximization of single variables, but their number can be very large. To efficiently and exhaustively find Pareto optimal solutions, we introduce a mapping between coloured Hasse diagrams and polytopes associated with an ideal point. A dynamic program based on edge contractions yields an exact closed-form description of the Pareto optimal set, in polynomial time of the number of objectives relative to the number of faces of the Pareto front. We additionnally discuss the special case of series-parallel graphs with monochromatic connected components of bounded size, for which the running time and the representation of solutions can in principle be linear in the number of objectives.

We formulate a dynamical model for microtubules interacting with a catastrophe-inducing boundary. In this model microtubules are either waiting to be nucleated, actively growing or shrinking, or stalled at the boundary. We first determine the steady-state occupation of these various states and the resultant length distribution. Next, we formulate the problem of the Mean First-Passage Time to reach the boundary in terms of an appropriate set of splitting probabilities and conditional Mean First-Passage Times, and solve explicitly for these quantities using a differential equation approach. As an application, we revisit a recently proposed search-and-capture model for the interaction between microtubules and target chromosomes [Gopalakrishnan & Govindan, Bull. Math. Biol. 73:2483--506 (2011)]. We show how our approach leads to a direct and compact solution of this problem.

Inspired by recent experiments on the spatial organization of bacterial chromosomes, we consider a type of "bottle brush" polymer consisting of a flexible backbone chain, to which flexible side loops are connected. We show that such a model with an open linear backbone spontaneously adopts a helical structure with a well-defined pitch when confined to small cylindrical volume. This helicity persists over a range of sizes and aspect-ratios of the cylinder, provided the packing fraction of the chain is suitably large. We analyze this results in terms of the interplay between the effective stiffness and actual intra-chain packing effects caused by the side-loops in response to the confinement. For the case of a circular backbone, mimicking e.g. the E. coli chromosome, the polymer adopts a linearized configuration of two parallel helices connected at the cylinder poles., Comment: paper and supplementary; 7 pages, 8 figures

Microtubules are highly regulated dynamic elements of the cytoskeleton of eukaryotic cells. One of the regulation mechanisms observed in living cells is the severing by the proteins katanin and spastin. We introduce a model for the dynamics of microtubules in the presence of randomly occurring severing events. Under the biologically motivated assumption that the newly created plus end undergoes a catastrophe, we investigate the steady state length distribution. We show that the presence of severing does not affect the number of microtubules, regardless of the distribution of severing events. In the special case in which the microtubules cannot recover from the depolymerizing state (no rescue events) we derive an analytical expression for the length distribution. In the general case we transform the problem into a single ODE that is solved numerically., Comment: 9 pages, 4 figures

DNA-coated colloids are a popular model system for self-assembly through tunable interactions. The DNA-encoded linkages between particles theoretically allow for very high specificity, but generally no directionality or long-range interactions. We introduce a two-dimensional lattice model for particles of many different types with short-range isotropic interactions that are pairwise specific. For this class of models, we address the fundamental question whether it is possible to reliably design the interactions so that the ground state is unique and corresponds to a given crystal structure. First, we determine lower limits for the interaction range between particles, depending on the complexity of the desired pattern and the underlying lattice. Then, we introduce a `recipe' for determining the pairwise interactions that exactly satisfies this minimum criterion, and we show that it is sufficient to uniquely determine the ground state for a large class of crystal structures. Finally, we verify these results using Monte Carlo simulations., Comment: 19 pages, 7 figures

The cortical array is a structure consisting of highly aligned microtubules which plays a crucial role in the characteristic uniaxial expansion of all growing plant cells. Recent experiments have shown polymerization-driven collisions between the membrane-bound cortical microtubules, suggesting a possible mechanism for their alignment. We present both a coarse-grained theoretical model and stochastic particle-based simulations of this mechanism, and compare the results from these complementary approaches. Our results indicate that collisions that induce depolymerization are sufficient to generate the alignment of microtubules in the cortical array., Comment: 4+ pages, 3 figures v2: significantly revised the exposition of the analytical model and expanded the discussion on our choice for the collision outcome probabilities; clarified the scope of the conclusions; numerous smaller changes throughout

The plant microtubule cortical array is a striking feature of all growing plant cells. It consists of a more or less homogeneously distributed array of highly aligned microtubules connected to the inner side of the plasma membrane and oriented transversely to the cell growth axis. Here we formulate a continuum model to describe the origin of orientational order in such confined arrays of dynamical microtubules. The model is based on recent experimental observations that show that a growing cortical microtubule can interact through angle dependent collisions with pre-existing microtubules that can lead either to co-alignment of the growth, retraction through catastrophe induction or crossing over the encountered microtubule. We identify a single control parameter, which is fully determined by the nucleation rate and intrinsic dynamics of individual microtubules. We solve the model analytically in the stationary isotropic phase, discuss the limits of stability of this isotropic phase, and explicitly solve for the ordered stationary states in a simplified version of the model., Comment: 15 pages, 5 figures

Whereas entropy can induce phase behavior that is as rich as seen in energetic systems, microphase separation remains a very rare phenomenon in entropic systems. In this paper, we present a density functional approach to study the possibility of entropy-driven microphase separation in diblock copolymers. Our model system consists of copolymers composed of freely-jointed slender hard rods. The two types of monomeric segments have comparable lengths, but a significantly different diameter, the latter difference providing the driving force for the phase separation. At the same time these systems can also exhibit liquid crystalline phases. We treat this system in the appropriate generalization of the Onsager approximation to chain-like particles. Using a linear stability (bifurcation) analysis, we analytically determine the onset of the microseparated and the nematic phases for long chains. We find that for very long chains the microseparated phase always preempts the nematic. In the limit of infinitely long chains, the correlations within the chain become Gaussian and the approach becomes exact. This allows us to define a Gaussian limit in which the theory strongly simplifies and the competition between microphase separation and liquid crystal formation can be studied essentially analytically. Our main results are phase diagrams as a function of the effective diameter difference, the segment composition and the length ratio of the segments. We also determine the amplitude of the positional order as a function of position along the chain at the onset of the microphase separation instability. Finally, we give suggestions as to how this type of entropy-induced microphase separation could be observed experimentally., Comment: 16 pages, 7 figures

We investigate the phase behavior of tetrapods, hard non-convex bodies formed by 4 rods connected under tetrahedral angles. We predict that, depending on the relative lengths of the rods these particles can form a uniaxial nematic phase, and more surprisingly they can exhibit a cubatic phase, a special case of the biaxial nematic phase. These predictions may be experimentally testable, as experimental realizations of tetrapods have recently become available., Comment: 8 pages ReVTeX 4, including 3 EPS figures

We investigate the possibility that freely rotating cylinders with an aspect ratio $L/D=0.9$ exhibit a cubatic phase similar to the one found for a system of cut-spheres. We present theoretical arguments why a cubatic phase might occur in this particular system. Monte Carlo simulations do not confirm the existence of a cubatic phase for cylinders. However, they do reveal an unexpected phase behavior between the isotropic and crystalline phase., Comment: 24 pages, 12 figures, RevTex (Submitted to J. Chem. Phys.)