2,912 research outputs found
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
Correlated dynamics of inclusions in a supported membrane
The hydrodynamic theory of heterogeneous fluid membranes is extended to the
case of a membrane adjacent to a solid substrate. We derive the coupling
diffusion coefficients of pairs of membrane inclusions in the limit of large
separation compared to the inclusion size. Two-dimensional compressive stresses
in the membrane make the coupling coefficients decay asymptotically as
with interparticle distance . For the common case, where the distance to the
substrate is of sub-micron scale, we present expressions for the coupling
between distant disklike inclusions, which are valid for arbitrary inclusion
size. We calculate the effect of inclusions on the response of the membrane and
the associated corrections to the coupling diffusion coefficients to leading
order in the concentration of inclusions. While at short distances the response
is modified as if the membrane were a two-dimensional suspension, the
large-distance response is not renormalized by the inclusions.Comment: 15 page
Steady-state simulations using weighted ensemble path sampling
We extend the weighted ensemble (WE) path sampling method to perform rigorous
statistical sampling for systems at steady state. The straightforward
steady-state implementation of WE is directly practical for simple landscapes,
but not when significant metastable intermediates states are present. We
therefore develop an enhanced WE scheme, building on existing ideas, which
accelerates attainment of steady state in complex systems. We apply both WE
approaches to several model systems confirming their correctness and efficiency
by comparison with brute-force results. The enhanced version is significantly
faster than the brute force and straightforward WE for systems with WE bins
that accurately reflect the reaction coordinate(s). The new WE methods can also
be applied to equilibrium sampling, since equilibrium is a steady state
Fluctuation induced interactions between domains in membranes
We study a model lipid bilayer composed of a mixture of two incompatible
lipid types which have a natural tendency to segregate in the absence of
membrane fluctuations. The membrane is mechanically characterized by a local
bending rigidity which varies with the average local lipid
composition . We show, in the case where varies weakly with
, that the effective interaction between lipids of the same type can
either be everywhere attractive or can have a repulsive component at
intermediate distances greater than the typical lipid size. When this
interaction has a repulsive component, it can prevent macro-phase separation
and lead to separation in mesophases with a finite domain size. This effect
could be relevant to certain experimental and numerical observations of
mesoscopic domains in such systems.Comment: 9 pages RevTex, 1 eps figur
Stability domains of actin genes and genomic evolution
In eukaryotic genes the protein coding sequence is split into several
fragments, the exons, separated by non-coding DNA stretches, the introns.
Prokaryotes do not have introns in their genome. We report the calculations of
stability domains of actin genes for various organisms in the animal, plant and
fungi kingdoms. Actin genes have been chosen because they have been highly
conserved during evolution. In these genes all introns were removed so as to
mimic ancient genes at the time of the early eukaryotic development, i.e.
before introns insertion. Common stability boundaries are found in evolutionary
distant organisms, which implies that these boundaries date from the early
origin of eukaryotes. In general boundaries correspond with introns positions
of vertebrates and other animals actins, but not much for plants and fungi. The
sharpest boundary is found in a locus where fungi, algae and animals have
introns in positions separated by one nucleotide only, which identifies a
hot-spot for insertion. These results suggest that some introns may have been
incorporated into the genomes through a thermodynamic driven mechanism, in
agreement with previous observations on human genes. They also suggest a
different mechanism for introns insertion in plants and animals.Comment: 9 Pages, 7 figures. Phys. Rev. E in pres
Stiff Polymers, Foams and Fiber Networks
We study the elasticity of fibrous materials composed of generalized stiff
polymers. It is shown that in contrast to cellular foam-like structures affine
strain fields are generically unstable. Instead, a subtle interplay between the
architecture of the network and the elastic properties of its building blocks
leads to intriguing mechanical properties with intermediate asymptotic scaling
regimes. We present exhaustive numerical studies based on a finite element
method complemented by scaling arguments.Comment: 4 pages, 5 figure
The mechanical response of semiflexible networks to localized perturbations
Previous research on semiflexible polymers including cytoskeletal networks in
cells has suggested the existence of distinct regimes of elastic response, in
which the strain field is either uniform (affine) or non-uniform (non-affine)
under external stress. Associated with these regimes, it has been further
suggested that a new fundamental length scale emerges, which characterizes the
scale for the crossover from non-affine to affine deformations. Here, we extend
these studies by probing the response to localized forces and force dipoles. We
show that the previously identified nonaffinity length [D.A. Head et al. PRE
68, 061907 (2003).] controls the mesoscopic response to point forces and the
crossover to continuum elastic behavior at large distances.Comment: 16 pages, 18 figures; substantial changes to text and figures to
clarify the crossover to continuum elasticity and the role of finite-size
effect
Clustered bottlenecks in mRNA translation and protein synthesis
We construct an algorithm that generates large, band-diagonal transition
matrices for a totally asymmetric exclusion process (TASEP) with local hopping
rate inhomogeneities. The matrices are diagonalized numerically to find
steady-state currents of TASEPs with local variations in hopping rate. The
results are then used to investigate clustering of slow codons along mRNA.
Ribosome density profiles near neighboring clusters of slow codons interact,
enhancing suppression of ribosome throughput when such bottlenecks are closely
spaced. Increasing the slow codon cluster size, beyond , does not
significantly reduce ribosome current. Our results are verified by extensive
Monte-Carlo simulations and provide a biologically-motivated explanation for
the experimentally-observed clustering of low-usage codons
Fluctuation-Induced Interactions between Rods on Membranes and Interfaces
We consider the interaction between two rods embedded in a fluctuating
surface which is governed by either surface tension or rigidity. The
modification of fluctuations by the rods leads to an attractive long-range
interaction that falls off as with their separation. The orientational
dependence of the resulting interaction is non-trivial and may lead to
interesting patterns of rod-like objects on such surfaces.Comment: Revtex, 10 pages, one figur
Selective Inhibitors of 11β-Hydroxysteroid Dehydrogenase Type 1 for Patients With Metabolic Syndrome: Is the Target Liver, Fat, or Both?
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