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Self-assembly of functional branched filaments, such as actin filaments and microtubules, or dysfunctional ones, such as amyloid fibrils, plays important roles in many biological processes. Here, based on the master equation approach, we study the kinetics of the formation of the branched fibrils. In our model, a branched fibril has one mother branch and several daughter branches. A daughter branch grows from the side of a pre-existing mother branch or daughter branch. In our model, we consider five basic processes for the self-assembly of the branched filaments, namely, the nucleation, the dissociation of the primary nucleus of fibrils, the elongation, the fragmentation, and the branching. The elongation of a mother branch from two ends and the elongation of a daughter branch from two ends can, in principle, occur with four different rate constants associated with the corresponding tips. This leads to a pronounced impact of the directionality of growth on the kinetics of the self-assembly. Here, we have unified and generalized our four previously presented models of branched fibrillogenesis in a single model. We have obtained a system of non-linear ordinary differential equations that give the time evolution of the polymer numbers and the mass concentrations along with the higher moments as observable quantities.

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Quite often polymers exhibit different elastic behavior depending on the statistical ensemble (Gibbs vs. Helmholtz). This is an effect of strong fluctuations. In particular, two-state polymers, which locally or globally fluctuate between two classes of microstates, can exhibit strong ensemble inequivalence with negative elastic moduli (extensibility or compressibility) in the Helmholtz ensemble. Two-state polymers consisting of flexible beads and springs have been studied extensively. Recently, similar behavior was predicted in a strongly stretched wormlike chain consisting of a sequence of reversible blocks, fluctuating between two values of the bending stiffness (the so called reversible wormlike chain, rWLC). In this article, we theoretically analyse the elasticity of a grafted rod-like semiflexible filament which fluctuates between two states of bending stiffness. We consider the response to a point force at the fluctuating tip in both the Gibbs and the Helmholtz ensemble. We also calculate the entropic force exerted by the filament on a confining wall. This is done in the Helmholtz ensemble and, under certain conditions, it yields negative compressibility. We consider a two-state homopolymer and a two-block copolymer with two-state blocks. Possible physical realizations of such a system would be grafted DNA or carbon nanorods undergoing hybridization, or grafted F-actin bundles undergoing collective reversible unbinding.

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Semiflexible nunchucks are block copolymers, which consist of two long blocks of high bending stiffness jointed together by a short block of low bending stiffness. Semiflexible nunchucks that consist of two DNA nanorods jointed by a short segment of double-stranded (ds) DNA and confined in two dimensions have been used in recent experiments by Fygenson and coworkers as a tool to magnify the bending fluctuations of the linking dsDNA, which in turn are used to deduce the persistence length of dsDNA. In a recent theoretical analysis, we showed that in a semiflexible nunchuck with one end grafted, the fluctuations of the position of the free end that is transverse to the grafting direction exhibit a pronounced bimodality, provided that the bending stiffness of the hinge is not very large. In this article, we theoretically analyse a grafted semiflexible nunchuck with a magnetic bead attached to its free end. We show that a transverse magnetic field induces an asymmetry in the bimodal distribution of the transverse fluctuations of the free end. This asymmetry is very sensitive to interactions with a magnetic field and, in principle, could be used in magnetometry (the measurement of a magnetic field or the magnetic moment of the bead). We also investigate how the response of the bimodal distribution of the transverse fluctuations of the free end to a magnetic field depends on the bending stiffness of the nunchuck hinge. In addition, we analyse the closely related systems of a single filament and two filaments jointed at a kink point with one end grafted and the other end attached to a magnetic bead.

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Kinks can appear along the contour of semiflexible polymers (biopolymers or synthetic ones), and they affect their elasticity and function. A regular sequence of alternating kink defects can form a semiflexible nanospring. In this article, we theoretically analyze the elastic behavior of such a nanospring with a point magnetic dipole attached to one end while the other end is assumed to be grafted to a rigid substrate. The rod-like segments of the nanospring are treated as weakly bending wormlike chains, and the propagator (Green's function) method is used in order to calculate the conformational and elastic properties of this system. We analytically calculate the distribution of orientational and positional fluctuations of the free end, the force-extension relation, as well as the compressional force that such a spring can exert on a planar wall. Our results show how the magnetic interaction affects the elasticity of the semiflexible nanospring. This sensitivity, which is based on the interplay of positional and orientational degrees of freedom, may prove useful in magnetometry or other applications.

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Semiflexible nunchucks are block copolymers consisting of two long blocks with high bending rigidity jointed by a short block of lower bending stiffness. Recently, the DNA nanotube nunchuck was introduced as a simple nanoinstrument that mechanically magnifies the bending angle of short double-stranded (ds) DNA and allows its measurement in a straightforward way [Fygenson et al., Nano Lett. 2020, 20, 2, 1388-1395]. It comprises two long DNA nanotubes linked by a dsDNA segment, which acts as a hinge. The semiflexible nunchuck geometry also appears in dsDNA with a hinge defect (e.g., a quenched denaturation bubble or a nick), and in end-linked stiff filaments. In this article, we theoretically investigate various aspects of the conformations and the tensile elasticity of semiflexible nunchucks. We analytically calculate the distribution of bending fluctuations of a wormlike chain (WLC) consisting of three blocks with different bending stiffness. For a system of two weakly bending WLCs end-jointed by a rigid kink, with one end grafted, we calculate the distribution of positional fluctuations of the free end. For a system of two weakly bending WLCs end-jointed by a hinge modeled as harmonic bending spring, with one end grafted, we calculate the positional fluctuations of the free end. We show that, under certain conditions, there is a pronounced bimodality in the transverse fluctuations of the free end. For a semiflexible nunchuck under tension, under certain conditions, there is bimodality in the extension as a function of the hinge position. We also show how steric repulsion affects the bending fluctuations of a rigid-rod nunchuck.

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Using the positional-orientational propagator of a semiflexible filament in the weakly bending regime, we analytically calculate the probability densities associated with the fluctuating tip and the corners of a grafted system of connected quadrilaterals. We calculate closed analytic expressions for the probability densities within the framework of the worm-like chain model, which are valid in the weakly bending regime. The probability densities give the physical quantities related to the elasticity of the system such as the force-extension relation in the fixed extension ensemble, the Poisson's ratio and the average of the force exerted to a confining stiff planar wall by the fluctuating tip of the system. Our analysis reveals that the force-extension relations depend on the contour length of the system (material content), the bending stiffness (chemical nature), the geometrical angle and the number of the quadrilaterals, while the Poisson's ratio depends only on the geometrical angle and the number of the quadrilaterals, and is thus a purely geometric property of the system.

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The self-assembly of fibrils is a subject of intense interest, primarily due to its relevance to the formation of pathological structures. Some fibrils develop branches via the so-called secondary nucleation. In this paper, we use the master equation approach to model the kinetics of formation of branched fibrils. In our model, a branched fibril consists of one mother branch and several daughter branches. We consider five basic processes of fibril formation, namely, nucleation, elongation, branching, fragmentation, and dissociation of the primary nucleus of fibrils into free monomers. Our main focus is on the effect of the directionality of growth on the kinetics of fibril formation. We consider several cases. At first, the mother branch may elongate from one or from both ends, while the daughter branch elongates only from one end. We also study the case of branched fibrils with bidirectionally growing daughter branches, tangentially to the main stem, which resembles the intertwining process. We derive a set of ordinary differential equations for the moments of the number concentration of fibrils, which can be solved numerically. Assuming that the primary nucleus of fibrils dissociates with the fragmentation rate, in the limit of the zero branching rate, our model reproduces the results of a previous model that considers only the three basic processes of nucleation, elongation, and fragmentation. We also use the experimental parameters for the fibril formation of Huntingtin fragments to investigate the effect of unidirectional vs bidirectional elongation of the filaments on the kinetics of fibrillogenesis.

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Using the first passage method for a Markov process, we theoretically study the fragmentation rate of a discrete one-dimensional chain (Rouse model). The fragmentation occurs due to thermal fluctuations. Assuming equilibrium initial conditions, we obtain an expression for the fragmentation rate of the one-dimensional filament as a function of the number of monomers, the position of the breaking point along the filament, the ratio of the bond energy to the thermal energy, and the Rouse relaxation time. We also obtain the fragmentation rate for a fixed initial configuration of the chain by numerically solving a Volterra equation. Our results reduce to those of previous theoretical studies at the appropriate limits, and spell out the role of the relevant time scales. The prediction of our model for the fragmentation rate of insulin fibrils under optimal growth conditions for the solution appears to be consistent with experimental data from other studies.

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We analyze the stretching elasticity of a wormlike chain with a tension discontinuity resulting from a Hookean spring connecting its backbone to a fixed point. The elasticity of isolated semiflexible filaments has been the subject in a significant body of literature, primarily because of its relevance to the mechanics of biological matter. In real systems, however, these filaments are usually part of supramolecular structures involving cross-linkers or molecular motors, which cause tension discontinuities. Our model is intended as a minimal structural element incorporating such a discontinuity. We obtain analytical results in the weakly bending limit of the filament, concerning its force-extension relation and the response of the two parts in which the filament is divided by the spring. For a small tension discontinuity, the linear response of the filament extension to this discontinuity strongly depends on the external tension. For large external tension f, the spring force contributes a subdominant correction ∼1/f^{3/2} to the well-known ∼1/sqrt[f]-dependence of the end-to-end extension.

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Cells moving on a two dimensional substrate generate motion by polymerizing actin filament networks inside a flat membrane protrusion. New filaments are generated by branching off existing ones, giving rise to branched network structures. We investigate the force-extension relation of branched filaments, grafted on an elastic structure at one end and pushing with the free ends against the leading edge cell membrane. Single filaments are modeled as worm-like chains, whose thermal bending fluctuations are restricted by the leading edge cell membrane, resulting in an effective force. Branching can increase the stiffness considerably; however the effect depends on branch point position and filament orientation, being most pronounced for intermediate tilt angles and intermediate branch point positions. We describe filament networks without cross-linkers to focus on the effect of branching. We use randomly positioned branch points, as generated in the process of treadmilling, and orientation distributions as measured in lamellipodia. These networks reproduce both the weak and strong force response of lamellipodia as measured in force-velocity experiments. We compare properties of branched and unbranched networks. The ratio of the network average of the force per branched filament to the average force per unbranched filament depends on the orientation distribution of the filaments. The ratio exhibits compression dependence and may go up to about 4.5 in networks with a narrow orientation distribution. With orientation distributions measured in lamellipodia, it is about two and essentially independent from network compression, graft elasticity and filament persistence length.

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