358 research outputs found
Release of Hemoglobin and Potassium from Human Red Blood Cells Treated with Triton X-100 Under the Critical Micellar Concentration
The action of detergents is thought to be connected primarily with micelle formation. However, detergent monomers can also effect biological systems. It was found in this study that human red blood cells can be disintegrated with Triton X-100 non-ionic detergent at a concentration of 0.007 %, lower than the critical micellar concentration (CMC). The time dependent release of hemoglobin and potassium was detected at 37°C and both were sigmoid in character. Although potassium was released faster than hemoglobin, a cooperative relationship between potassium and hemoglobin within the intact red blood cell is suggested by this observation
Extracting Structural Information of a Heteropolymer from Force-Extension Curves
We present a theory for the reverse analysis on the sequence information of a
single H/P two-letter random hetero-polymer (RHP) from its force-extension(f-z)
curves during quasi static stretching. Upon stretching of a self-assembled RHP,
it undergoes several structural transitions. The typical elastic response of a
hetero-polymeric globule is a set of overlapping saw-tooth patterns. With
consideration of the height and the position of the overlapping saw-tooth
shape, we analyze the possibility of extracting the binding energies of the
internal domains and the corresponding block sizes of the contributing
conformations.Comment: 5 figures 7 page
A Quantitative Theory of Mechanical Unfolding of a Homopolymer Globule
We propose the quantitative mean-field theory of mechanical unfolding of a
globule formed by long flexible homopolymer chain collapsed in poor solvent and
subjected to extensional deformation. We demonstrate that depending on the
degree of polymerization and solvent quality (quantified by the Flory-Huggins
parameter) the mechanical unfolding of the collapsed chain may either
occur continuously (by passing a sequence of uniformly elongated
configurations) or involves intra-molecular micro-phase coexistence of a
collapsed and a stretched segment followed by an abrupt unraveling transition.
The force-extension curves are obtained and quantitatively compared to our
recent results of numerical self-consistent field (SCF) simulations. The phase
diagrams for extended homopolymer chains in poor solvent comprising one- and
two-phase regions are calculated for different chain length or/and solvent
quality.Comment: 24 pages, 18 figure
Nanomechanics combined with HDX reveals allosteric drug binding sites of CFTR NBD1.
Cystic fibrosis (CF) is a frequent genetic disease in Caucasians that is caused by the deletion of F508 (DF508) in the nucleotide binding domain 1 (NBD1) of the CF transmembrane conductance regulator (CFTR). The DF508 compromises the folding energetics of the NBD1, as well as the folding of three other CFTR domains. Combination of FDA approved corrector molecules can efficiently but incompletely rescue the DF508-CFTR folding and stability defect. Thus, new pharmacophores that would reinstate the wild-type-like conformational stability of the DF508-NBD1 would be highly beneficial. The most prominent molecule, 5-bromoindole-3-acetic acid (BIA) that can thermally stabilize the NBD1 has low potency and efficacy. To gain insights into the NBD1 (un)folding dynamics and BIA binding site localization, we combined molecular dynamics (MD) simulations, atomic force spectroscopy (AFM) and hydrogen- deuterium exchange (HDX) experiments. We found that the NBD1 a-subdomain with three adjacent strands from the b-subdomain plays an important role in early folding steps, when crucial non-native interactions are formed via residue F508. Our AFM and HDX experiments showed that BIA associates with this a-core region and increases the resistance of the DF508-NBD1 against mechanical unfolding, a phenomenon that could be exploited in future developments of folding correctors
Dynamics of folding in Semiflexible filaments
We investigate the dynamics of a single semiflexible filament, under the
action of a compressing force, using numerical simulations and scaling
arguments. The force is applied along the end to end vector at one extremity of
the filament, while the other end is held fixed. We find that, unlike in
elastic rods the filament folds asymmetrically with a folding length which
depends only on the bending stiffness and the applied force. It is shown that
this behavior can be attributed to the exponentially falling tension profile in
the filament. While the folding time depends on the initial configuration, at
late time, the distance moved by the terminal point of the filament and the
length of the fold shows a power law dependence on time with an exponent 1/2.Comment: 13 pages, Late
Muscle thixotropy: more than just cross-bridges?
AbstractAlthough Campbell and Lakie in a Comment to the Editor in this issue of Biophysical Journal suggested that exclusive cross-bridge action is behind muscle thixotropy, recent findings and our preliminary observations suggest that additional mechanisms could also be involved
Effective Area-Elasticity and Tension of Micro-manipulated Membranes
We evaluate the effective Hamiltonian governing, at the optically resolved
scale, the elastic properties of micro-manipulated membranes. We identify
floppy, entropic-tense and stretched-tense regimes, representing different
behaviors of the effective area-elasticity of the membrane. The corresponding
effective tension depends on the microscopic parameters (total area, bending
rigidity) and on the optically visible area, which is controlled by the imposed
external constraints. We successfully compare our predictions with recent data
on micropipette experiments.Comment: To be published in Phys. Rev. Let
Stretched Polymers in a Poor Solvent
Stretched polymers with attractive interaction are studied in two and three
dimensions. They are described by biased self-avoiding random walks with
nearest neighbour attraction. The bias corresponds to opposite forces applied
to the first and last monomers. We show that both in and a phase
transition occurs as this force is increased beyond a critical value, where the
polymer changes from a collapsed globule to a stretched configuration. This
transition is second order in and first order in . For we
predict the transition point quantitatively from properties of the unstretched
polymer. This is not possible in , but even there we can estimate the
transition point precisely, and we can study the scaling at temperatures
slightly below the collapse temperature of the unstretched polymer. We find
very large finite size corrections which would make very difficult the estimate
of the transition point from straightforward simulations.Comment: 10 pages, 16 figure
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