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

Insight into Resonant Activation in Discrete Systems

The resonant activation phenomenon (RAP) in a discrete system is studied using the master equation formalism. We show that the RAP corresponds to a non-monotonic behavior of the frequency dependent first passage time probability density function (pdf). An analytical expression for the resonant frequency is introduced, which, together with numerical results, helps understand the RAP behavior in the space spanned by the transition rates for the case of reflecting and absorbing boundary conditions. The limited range of system parameters for which the RAP occurs is discussed. We show that a minimum and a maximum in the mean first passage time (MFPT) can be obtained when both boundaries are absorbing. Relationships to some biological systems are suggested.Comment: 5 pages, 5 figures, Phys. Rev. E., in pres

Effect of dipolar moments in domain sizes of lipid bilayers and monolayers

Lipid domains are found in systems such as multi-component bilayer membranes and single component monolayers at the air-water interface. It was shown by Andelman et al. (Comptes Rendus 301, 675 (1985)) and McConnell et al. (Phys. Chem. {\bf 91}, 6417 (1987)) that in monolayers, the size of the domains results from balancing the line tension, which favors the formation of a large single circular domain, against the electrostatic cost of assembling the dipolar moments of the lipids. In this paper, we present an exact analytical expression for the electric potential, ion distribution and electrostatic free energy for different problems consisting of three different slabs with different dielectric constants and Debye lengths, with a circular homogeneous dipolar density in the middle slab. From these solutions, we extend the calculation of domain sizes for monolayers to include the effects of finite ionic strength, dielectric discontinuities (or image charges) and the polarizability of the dipoles and further generalize the calculations to account for domains in lipid bilayers. In monolayers, the size of the domains is dependent on the different dielectric constants but independent of ionic strength. In asymmetric bilayers, where the inner and outer leaflets have different dipolar densities, domains show a strong size dependence with ionic strength, with molecular-sized domains that grow to macroscopic phase separation with increasing ionic strength. We discuss the implications of the results for experiments and briefly consider their relation to other two dimensional systems such as Wigner crystals or heteroepitaxial growth.Comment: 13 pages, 5 figues in eps Replaced with new version, one citation added and a few statements corrected. The results of the paper are unchange

Effective Medium Theory of Filamentous Triangular Lattice

We present an effective medium theory that includes bending as well as stretching forces, and we use it to calculate mechanical response of a diluted filamentous triangular lattice. In this lattice, bonds are central-force springs, and there are bending forces between neighboring bonds on the same filament. We investigate the diluted lattice in which each bond is present with a probability $p$. We find a rigidity threshold $p_b$ which has the same value for all positive bending rigidity and a crossover characterizing bending-, stretching-, and bend-stretch coupled elastic regimes controlled by the central-force rigidity percolation point at $p_{\textrm{CF}} \simeq 2/3$ of the lattice when fiber bending rigidity vanishes.Comment: 15 pages, 9 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

Surface tension in bilayer membranes with fixed projected area

We study the elastic response of bilayer membranes with fixed projected area to both stretching and shape deformations. A surface tension is associated to each of these deformations. By using model amphiphilic membranes and computer simulations, we are able to observe both the types of deformation, and thus, both the surface tensions, related to each type of deformation, are measured for the same system. These surface tensions are found to assume different values in the same bilayer membrane: in particular they vanish for different values of the projected area. We introduce a simple theory which relates the two quantities and successfully apply it to the data obtained with computer simulations

Bridging the microscopic and the hydrodynamic in active filament solutions

Hydrodynamic equations for an isotropic solution of active polar filaments are derived from a microscopic mean-field model of the forces exchanged between motors and filaments. We find that a spatial dependence of the motor stepping rate along the filament is essential to drive bundle formation. A number of differences arise as compared to hydrodynamics derived (earlier) from a mesoscopic model where relative filament velocities were obtained on the basis of symmetry considerations. Due to the anisotropy of filament diffusion, motors are capable of generating net filament motion relative to the solvent. The effect of this new term on the stability of the homogeneous state is investigated.Comment: 7 pages, 2 figures, submitted to Europhys. Let

Rheology of Active Filament Solutions

We study the viscoelasticity of an active solution of polar biofilaments and motor proteins. Using a molecular model, we derive the constitutive equations for the stress tensor in the isotropic phase and in phases with liquid crystalline order. The stress relaxation in the various phases is discussed. Contractile activity is responsible for a spectacular difference in the viscoelastic properties on opposite sides of the order-disorder transition.Comment: 4 pages, 1 figur

Spontaneous flow transition in active polar gels

We study theoretically the effects of confinement on active polar gels such as the actin network of eukaryotic cells. Using generalized hydrodynamics equations derived for active gels, we predict, in the case of quasi one-dimensional geometry, a spontaneous flow transition from a homogeneously polarized immobile state for small thicknesses, to a perturbed flowing state for larger thicknesses. The transition is not driven by an external field but by the activity of the system. We suggest several possible experimental realizations.Comment: 7 pages, 3 figures. To appear in Europhys. Let

Budding and vesiculation induced by conical membrane inclusions

Conical inclusions in a lipid bilayer generate an overall spontaneous curvature of the membrane that depends on concentration and geometry of the inclusions. Examples are integral and attached membrane proteins, viruses, and lipid domains. We propose an analytical model to study budding and vesiculation of the lipid bilayer membrane, which is based on the membrane bending energy and the translational entropy of the inclusions. If the inclusions are placed on a membrane with similar curvature radius, their repulsive membrane-mediated interaction is screened. Therefore, for high inclusion density the inclusions aggregate, induce bud formation, and finally vesiculation. Already with the bending energy alone our model allows the prediction of bud radii. However, in case the inclusions induce a single large vesicle to split into two smaller vesicles, bending energy alone predicts that the smaller vesicles have different sizes whereas the translational entropy favors the formation of equal-sized vesicles. Our results agree well with those of recent computer simulations.Comment: 11 pages, 12 figure