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

Melting of Branched RNA Molecules

Stability of the branching structure of an RNA molecule is an important condition for its function. In this letter we show that the melting thermodynamics of RNA molecules is very sensitive to their branching geometry for the case of a molecule whose groundstate has the branching geometry of a Cayley Tree and whose pairing interactions are described by the Go model. Whereas RNA molecules with a linear geometry melt via a conventional continuous phase transition with classical exponents, molecules with a Cayley Tree geometry are found to have a free energy that seems smooth, at least within our precision. Yet, we show analytically that this free energy in fact has a mathematical singularity at the stability limit of the ordered structure. The correlation length appears to diverge on the high-temperature side of this singularity.Comment: 4 pages, 3 figure

Anomalously Slow Domain Growth in Fluid Membranes with Asymmetric Transbilayer Lipid Distribution

The effect of asymmetry in the transbilayer lipid distribution on the dynamics of phase separation in fluid vesicles is investigated numerically for the first time. This asymmetry is shown to set a spontaneous curvature for the domains that alter the morphology and dynamics considerably. For moderate tension, the domains are capped and the spontaneous curvature leads to anomalously slow dynamics, as compared to the case of symmetric bilayers. In contrast, in the limiting cases of high and low tensions, the dynamics proceeds towards full phase separation.Comment: 4 pages, 5 figure

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

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

Mean encounter times for cell adhesion in hydrodynamic flow: analytical progress by dimensional reduction

For a cell moving in hydrodynamic flow above a wall, translational and rotational degrees of freedom are coupled by the Stokes equation. In addition, there is a close coupling of convection and diffusion due to the position-dependent mobility. These couplings render calculation of the mean encounter time between cell surface receptors and ligands on the substrate very difficult. Here we show for a two-dimensional model system how analytical progress can be achieved by treating motion in the vertical direction by an effective reaction term in the mean first passage time equation for the rotational degree of freedom. The strength of this reaction term can either be estimated from equilibrium considerations or used as a fit parameter. Our analytical results are confirmed by computer simulations and allow to assess the relative roles of convection and diffusion for different scaling regimes of interest.Comment: Reftex, postscript figures include

Domain Growth, Budding, and Fission in Phase Separating Self-Assembled Fluid Bilayers

A systematic investigation of the phase separation dynamics in self-assembled multi-component bilayer fluid vesicles and open membranes is presented. We use large-scale dissipative particle dynamics to explicitly account for solvent, thereby allowing for numerical investigation of the effects of hydrodynamics and area-to-volume constraints. In the case of asymmetric lipid composition, we observed regimes corresponding to coalescence of flat patches, budding, vesiculation and coalescence of caps. The area-to-volume constraint and hydrodynamics have a strong influence on these regimes and the crossovers between them. In the case of symmetric mixtures, irrespective of the area-to-volume ratio, we observed a growth regime with an exponent of 1/2. The same exponent is also found in the case of open membranes with symmetric composition

Coupled dynamics of RNA folding and nanopore translocation

The translocation of structured RNA or DNA molecules through narrow pores necessitates the opening of all base pairs. Here, we study the interplay between the dynamics of translocation and base-pairing theoretically, using kinetic Monte Carlo simulations and analytical methods. We find that the transient formation of basepairs that do not occur in the ground state can significantly speed up translocation.Comment: 4 pages, 3 figures, to appear in Physical Review Letter

Protein search for multiple targets on DNA

Protein-DNA interactions are crucial for all biological processes. One of the most important fundamental aspects of these interactions is the process of protein searching and recognizing specific binding sites on DNA. A large number of experimental and theoretical investigations have been devoted to uncovering the molecular description of these phenomena, but many aspects of the mechanisms of protein search for the targets on DNA remain not well understood. One of the most intriguing problems is the role of multiple targets in protein search dynamics. Using a recently developed theoretical framework we analyze this question in detail. Our method is based on a discrete-state stochastic approach that takes into account most relevant physical-chemical processes and leads to fully analytical description of all dynamic properties. Specifically, systems with two and three targets have been explicitly investigated. It is found that multiple targets in most cases accelerate the search in comparison with a single target situation. However, the acceleration is not always proportional to the number of targets. Surprisingly, there are even situations when it takes longer to find one of the multiple targets in comparison with the single target. It depends on the spatial position of the targets, distances between them, average scanning lengths of protein molecules on DNA, and the total DNA lengths. Physical-chemical explanations of observed results are presented. Our predictions are compared with experimental observations as well as with results from a continuum theory for the protein search. Extensive Monte Carlo computer simulations fully support our theoretical calculations

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