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

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

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

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

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

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

Nematic and Polar order in Active Filament Solutions

Using a microscopic model of interacting polar biofilaments and motor proteins, we characterize the phase diagram of both homogeneous and inhomogeneous states in terms of experimental parameters. The polarity of motor clusters is key in determining the organization of the filaments in homogeneous isotropic, polarized and nematic states, while motor-induced bundling yields spatially inhomogeneous structures.Comment: 4 pages. 3 figure

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

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

Testing Tensile and Shear Epoxy Strength at Cryogenic Temperatures

This paper covers cryogenic, tensile testing and research completed on a number of epoxies used in cryogenic applications. Epoxies are used in many different applications; however, this research focused on the use of epoxy used to bond MLI standoffs to cryogenic storage tanks and the loads imparted to the tank through the MLI. To conduct testing, samples were made from bare stainless steel, aluminum and primed aluminum. Testing involved slowly cooling test samples with liquid nitrogen then applying gradually increasing tensile loads to the epoxy. The testing evaluated the strength and durability of epoxies at cryogenic temperatures and serves as a base for future testing. The results of the tests showed that some epoxies withstood the harsh conditions while others failed. The two epoxies yielding the best results were Masterbond EP29LPSP and Scotch Weld 2216. For all metal surfaces tested, both epoxies had zero failures for up to 11.81 kg of mass