Molecular Electroporation and the Transduction of Oligoarginines

Certain short polycations, such as TAT and polyarginine, rapidly pass through the plasma membranes of mammalian cells by an unknown mechanism called transduction as well as by endocytosis and macropinocytosis. These cell-penetrating peptides (CPPs) promise to be medically useful when fused to biologically active peptides. I offer a simple model in which one or more CPPs and the phosphatidylserines of the inner leaflet form a kind of capacitor with a voltage in excess of 180 mV, high enough to create a molecular electropore. The model is consistent with an empirical upper limit on the cargo peptide of 40--60 amino acids and with experimental data on how the transduction of a polyarginine-fluorophore into mouse C2C12 myoblasts depends on the number of arginines in the CPP and on the CPP concentration. The model makes three testable predictions.Comment: 15 pages, 5 figure

Model for the unidirectional motion of a dynein molecule

Cytoplasmic dyneins transport cellular organelles by moving on a microtubule filament. It has been found recently that depending on the applied force and the concentration of the adenosine triphosphate (ATP) molecules, dynein's step size varies. Based on these studies, we propose a simple model for dynein's unidirectional motion taking into account the variations in its step size. We study how the average velocity and the relative dispersion in the displacement vary with the applied load. The model is amenable to further extensions by inclusion of details associated with the structure and the processivity of the molecule.Comment: 10 pages, 5 figure

Ribosome recycling induces optimal translation rate at low ribosomal availability

Funding statement The authors thank BBSRC (BB/F00513/X1, BB/I020926/1 and DTG) and SULSA for funding. Acknowledgement The authors thank R. Allen, L. Ciandrini, B. Gorgoni and P. Greulich for very helpful discussions and careful reading of the manuscript.Peer reviewedPublisher PD

Helicase activity on DNA as a propagating front

We develop a propagating front analysis, in terms of a local probability of zipping, for the helicase activity of opening up a double stranded DNA (dsDNA). In a fixed-distance ensemble (conjugate to the fixed-force ensemble) the front separates the zipped and unzipped phases of a dsDNA and a drive acts locally around the front. Bounds from variational analysis and numerical estimates for the speed of a helicase are obtained. Different types of helicase behaviours can be distinguished by the nature of the drive.Comment: 5 pages, 5 eps figures; replaced by the published versio

Phase Transitions in Multicomponent String Model

We propose a one-dimensional model of a string decorated with adhesion molecules (stickers) to mimic multicomponent membranes in restricted geometries. The string is bounded by two parallel walls and it interacts with one of them by short range attractive forces while the stickers are attracted by the other wall. The exact solution of the model in the case of infinite wall separation predicts both continuous and discontinuous transitions between phases characterised by low and high concentration of stickers on the string. Our model exhibits also coexistence of these two phases, similarly to models of multicomponent membranes.Comment: letter, 8 pages, 3 figure

Bidirectional transport on a dynamic lattice

Bidirectional variants of stochastic many particle models for transport by molecular motors show a strong tendency to form macroscopic clusters on static lattices. Inspired by the fact that the microscopic tracks for molecular motors are dynamical, we study the influence of different types of lattice dynamics on stochastic bidirectional transport. We observe a transition toward efficient transport (corresponding to the dissolution of large clusters) controlled by the lattice dynamics.Comment: 5 pages, 5 figure

Polymer Translocation Dynamics in the Quasi-Static Limit

Monte Carlo (MC) simulations are used to study the dynamics of polymer translocation through a nanopore in the limit where the translocation rate is sufficiently slow that the polymer maintains a state of conformational quasi-equilibrium. The system is modeled as a flexible hard-sphere chain that translocates through a cylindrical hole in a hard flat wall. In some calculations, the nanopore is connected at one end to a spherical cavity. Translocation times are measured directly using MC dynamics simulations. For sufficiently narrow pores, translocation is sufficiently slow that the mean translocation time scales with polymer length N according to \propto (N-N_p)^2, where N_p is the average number of monomers in the nanopore; this scaling is an indication of a quasi-static regime in which polymer-nanopore friction dominates. We use a multiple-histogram method to calculate the variation of the free energy with Q, a coordinate used to quantify the degree of translocation. The free energy functions are used with the Fokker-Planck formalism to calculate translocation time distributions in the quasi-static regime. These calculations also require a friction coefficient, characterized by a quantity N_{eff}, the effective number of monomers whose dynamics are affected by the confinement of the nanopore. This was determined by fixing the mean of the theoretical distribution to that of the distribution obtained from MC dynamics simulations. The theoretical distributions are in excellent quantitative agreement with the distributions obtained directly by the MC dynamics simulations for physically meaningful values of N_{eff}. The free energy functions for narrow-pore systems exhibit oscillations with an amplitude that is sensitive to the nanopore length. Generally, larger oscillation amplitudes correspond to longer translocation times.Comment: 13 pages, 13 figure

Dynamics of active membranes with internal noise

We study the time-dependent height fluctuations of an active membrane containing energy-dissipating pumps that drive the membrane out of equilibrium. Unlike previous investigations based on models that neglect either curvature couplings or random fluctuations in pump activities, our formulation explores two new models that take both of these effects into account. In the first model, the magnitude of the nonequilibrium forces generated by the pumps is allowed to fluctuate temporally. In the second model, the pumps are allowed to switch between "on" and "off" states. We compute the mean squared displacement of a membrane point for both models, and show that they exhibit distinct dynamical behaviors from previous models, and in particular, a superdiffusive regime specifically arising from the shot noise.Comment: 7 pages, 4 figure