123 research outputs found
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
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
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
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
Stretching of a polymer below the Theta point
The unfolding of a polymer below the point when pulled by an
external force is studied both in d=2 on the lattice and in off lattice.
A ground state analysis of finite length chains shows that the globule unfolds
via multiple steps, corresponding to transitions between different minima, in
both cases. In the infinite length limit, these intermediate minima have a
qualitative effect only in . The phase diagram in d=2 is determined using
transfer matrix techniques. Energy-entropy and renormalization group arguments
are given which predict a qualitatively correct phase diagram and a change of
the order of the transition from d=2 to d=3.Comment: 4 pages, 3 eps figure
Single Molecule Statistics and the Polynucleotide Unzipping Transition
We present an extensive theoretical investigation of the mechanical unzipping
of double-stranded DNA under the influence of an applied force. In the limit of
long polymers, there is a thermodynamic unzipping transition at a critical
force value of order 10 pN, with different critical behavior for homopolymers
and for random heteropolymers. We extend results on the disorder-averaged
behavior of DNA's with random sequences to the more experimentally accessible
problem of unzipping a single DNA molecule. As the applied force approaches the
critical value, the double-stranded DNA unravels in a series of discrete,
sequence-dependent steps that allow it to reach successively deeper energy
minima. Plots of extension versus force thus take the striking form of a series
of plateaus separated by sharp jumps. Similar qualitative features should
reappear in micromanipulation experiments on proteins and on folded RNA
molecules. Despite their unusual form, the extension versus force curves for
single molecules still reveal remnants of the disorder-averaged critical
behavior. Above the transition, the dynamics of the unzipping fork is related
to that of a particle diffusing in a random force field; anomalous,
disorder-dominated behavior is expected until the applied force exceeds the
critical value for unzipping by roughly 5 pN.Comment: 40 pages, 18 figure
Single-molecule experiments in biological physics: methods and applications
I review single-molecule experiments (SME) in biological physics. Recent
technological developments have provided the tools to design and build
scientific instruments of high enough sensitivity and precision to manipulate
and visualize individual molecules and measure microscopic forces. Using SME it
is possible to: manipulate molecules one at a time and measure distributions
describing molecular properties; characterize the kinetics of biomolecular
reactions and; detect molecular intermediates. SME provide the additional
information about thermodynamics and kinetics of biomolecular processes. This
complements information obtained in traditional bulk assays. In SME it is also
possible to measure small energies and detect large Brownian deviations in
biomolecular reactions, thereby offering new methods and systems to scrutinize
the basic foundations of statistical mechanics. This review is written at a
very introductory level emphasizing the importance of SME to scientists
interested in knowing the common playground of ideas and the interdisciplinary
topics accessible by these techniques. The review discusses SME from an
experimental perspective, first exposing the most common experimental
methodologies and later presenting various molecular systems where such
techniques have been applied. I briefly discuss experimental techniques such as
atomic-force microscopy (AFM), laser optical tweezers (LOT), magnetic tweezers
(MT), biomembrane force probe (BFP) and single-molecule fluorescence (SMF). I
then present several applications of SME to the study of nucleic acids (DNA,
RNA and DNA condensation), proteins (protein-protein interactions, protein
folding and molecular motors). Finally, I discuss applications of SME to the
study of the nonequilibrium thermodynamics of small systems and the
experimental verification of fluctuation theorems. I conclude with a discussion
of open questions and future perspectives.Comment: Latex, 60 pages, 12 figures, Topical Review for J. Phys. C (Cond.
Matt
Manipulating Protein Conformations By Single-molecule Afm-fret Nanoscopy
Combining atomic force microscopy and fluorescence resonance energy transfer spectroscopy (AFM-FRET), we have developed a single-molecule AFM-FRET nanoscopy approach capable of effectively pinpointing and mechanically manipulating a targeted dye-labeled single protein in a large sampling area and simultaneously monitoring the conformational changes of the targeted protein by recording single-molecule FRET time trajectories. We have further demonstrated an application of using this nanoscopy on manipulation of single-molecule protein conformation and simultaneous single-molecule FRET measurement of a Cy3-Cy5-labeled kinase enzyme, HPPK (6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase). By analyzing time-resolved FRET trajectories and correlated AFM force pulling curves of the targeted single-molecule enzyme, we are able to observe the protein conformational changes of a specific coordination by AFM mechanic force pulling
Gut Microbiota Is a Key Modulator of Insulin Resistance in TLR 2 Knockout Mice
A genetic and pharmacological approach reveals novel insights into how changes in gut microbiota can subvert genetically predetermined phenotypes from lean to obese
Force spectroscopy in studying infection
Biophysical force spectroscopy tools - for example optical tweezers, magnetic
tweezers, atomic force microscopy, - have been used to study elastic,
mechanical, conformational and dynamic properties of single biological
specimens from single proteins to whole cells to reveal information not
accessible by ensemble average methods such as X-ray crystallography, mass
spectroscopy, gel electrophoresis and so on. Here we review the application of
these tools on a range of infection-related questions from antibody-inhibited
protein processivity to virus-cell adhesion. In each case we focus on how the
instrumental design tailored to the biological system in question translates
into the functionality suitable for that particular study. The unique insights
that force spectroscopy has gained to complement knowledge learned through
population averaging techniques in interrogating biomolecular details prove to
be instrumental in therapeutic innovations such as those in structure-based
drug design
- …