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

Efficiency at maximum power of interacting molecular machines

We investigate the efficiency of systems of molecular motors operating at maximum power. We consider two models of kinesin motors on a microtubule: for both the simplified and the detailed model, we find that the many-body exclusion effect enhances the efficiency at maximum power of the many-motor system, with respect to the single motor case. Remarkably, we find that this effect occurs in a limited region of the system parameters, compatible with the biologically relevant range.Comment: To appear in Phys. Rev. Let

Non-equilibrium mechanics and dynamics of motor activated gels

The mechanics of cells is strongly affected by molecular motors that generate forces in the cellular cytoskeleton. We develop a model for cytoskeletal networks driven out of equilibrium by molecular motors exerting transient contractile stresses. Using this model we show how motor activity can dramatically increase the network's bulk elastic moduli. We also show how motor binding kinetics naturally leads to enhanced low-frequency stress fluctuations that result in non-equilibrium diffusive motion within an elastic network, as seen in recent \emph{in vitro} and \emph{in vivo} experiments.Comment: 21 pages, 8 figure

No many-scallop theorem: Collective locomotion of reciprocal swimmers

To achieve propulsion at low Reynolds number, a swimmer must deform in a way that is not invariant under time-reversal symmetry; this result is known as the scallop theorem. We show here that there is no many-scallop theorem. We demonstrate that two active particles undergoing reciprocal deformations can swim collectively; moreover, polar particles also experience effective long-range interactions. These results are derived for a minimal dimers model, and generalized to more complex geometries on the basis of symmetry and scaling arguments. We explain how such cooperative locomotion can be realized experimentally by shaking a collection of soft particles with a homogeneous external field

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

Time scale of entropic segregation of flexible polymers in confinement: Implications for chromosome segregation in filamentous bacteria

We report molecular dynamics simulations of the segregation of two overlapping chains in cylindrical confinement. We find that the entropic repulsion between the chains can be sufficiently strong to cause segregation on a time scale that is short compared to the one for diffusion. This result implies that entropic driving forces are sufficiently strong to cause rapid bacterial chromosome segregation.Comment: Minor changes. Added some references, corrected the labels in figure 6 and reformatted in two columns. Also added reference to published version in PR

Mechanics and force transmission in soft composites of rods in elastic gels

We report detailed theoretical investigations of the micro-mechanics and bulk elastic properties of composites consisting of randomly distributed stiff fibers embedded in an elastic matrix in two and three dimensions. Recent experiments published in Physical Review Letters [102, 188303 (2009)] have suggested that the inclusion of stiff microtubules in a softer, nearly incompressible biopolymer matrix can lead to emergent compressibility. This can be understood in terms of the enhancement of the compressibility of the composite relative to its shear compliance as a result of the addition of stiff rod-like inclusions. We show that the Poisson's ratio $\nu$ of such a composite evolves with increasing rod density towards a particular value, or {\em fixed point}, independent of the material properties of the matrix, so long as it has a finite initial compressibility. This fixed point is $\nu=1/4$ in three dimensions and $\nu=1/3$ in two dimensions. Our results suggest an important role for stiff filaments such as microtubules and stress fibers in cell mechanics. At the same time, our work has a wider elasticity context, with potential applications to composite elastic media with a wide separation of scales in stiffness of its constituents such as carbon nanotube-polymer composites, which have been shown to have highly tunable mechanics.Comment: 10 pages, 8 figure

Are stress-free membranes really 'tensionless'?

In recent years it has been argued that the tension parameter driving the fluctuations of fluid membranes, differs from the imposed lateral stress, the 'frame tension'. In particular, stress-free membranes were predicted to have a residual fluctuation tension. In the present paper, this argument is reconsidered and shown to be inherently inconsistent -- in the sense that a linearized theory, the Monge model, is used to predict a nonlinear effect. Furthermore, numerical simulations of one-dimensional stiff membranes are presented which clearly demonstrate, first, that the internal 'intrinsic' stress in membranes indeed differs from the frame tension as conjectured, but second, that the fluctuations are nevertheless driven by the frame tension. With this assumption, the predictions of the Monge model agree excellently with the simulation data for stiffness and tension values spanning several orders of magnitude