262 research outputs found
Collective effects in cellular structure formation mediated by compliant environments: a Monte Carlo study
Compliant environments can mediate interactions between mechanically active
cells like fibroblasts. Starting with a phenomenological model for the
behaviour of single cells, we use extensive Monte Carlo simulations to predict
non-trivial structure formation for cell communities on soft elastic substrates
as a function of elastic moduli, cell density, noise and cell position
geometry. In general, we find a disordered structure as well as ordered
string-like and ring-like structures. The transition between ordered and
disordered structures is controlled both by cell density and noise level, while
the transition between string- and ring-like ordered structures is controlled
by the Poisson ratio. Similar effects are observed in three dimensions. Our
results suggest that in regard to elastic effects, healthy connective tissue
usually is in a macroscopically disordered state, but can be switched to a
macroscopically ordered state by appropriate parameter variations, in a way
that is reminiscent of wound contraction or diseased states like contracture.Comment: 45 pages, 7 postscript figures included, revised version accepted for
publication in Acta Biomateriali
Focal adhesions as mechanosensors: the two-spring model
Adhesion-dependent cells actively sense the mechanical properties of their
environment through mechanotransductory processes at focal adhesions, which are
integrin-based contacts connecting the extracellular matrix to the
cytoskeleton. Here we present first steps towards a quantitative understanding
of focal adhesions as mechanosensors. It has been shown experimentally that
high levels of force are related to growth of and signaling at focal adhesions.
In particular, activation of the small GTPase Rho through focal adhesions leads
to the formation of stress fibers. Here we discuss one way in which force might
regulate the internal state of focal adhesions, namely by modulating the
internal rupture dynamics of focal adhesions. A simple two-spring model shows
that the stiffer the environment, the more efficient cellular force is built up
at focal adhesions by molecular motors interacting with the actin filaments.Comment: Latex, 17 pages, 5 postscript figures include
Effect of adhesion geometry and rigidity on cellular force distributions
The behaviour and fate of tissue cells is controlled by the rigidity and
geometry of their adhesive environment, possibly through forces localized to
sites of adhesion. We introduce a mechanical model that predicts cellular force
distributions for cells adhering to adhesive patterns with different geometries
and rigidities. For continuous adhesion along a closed contour, forces are
predicted to be localized to the corners. For discrete sites of adhesion, the
model predicts the forces to be mainly determined by the lateral pull of the
cell contour. With increasing distance between two neighboring sites of
adhesion, the adhesion force increases because cell shape results in steeper
pulling directions. Softer substrates result in smaller forces. Our predictions
agree well with experimental force patterns measured on pillar assays.Comment: 4 pages, Revtex with 4 figure
Focal adhesions as mechanosensors: the two-spring model
Adhesion-dependent cells actively sense the mechanical properties of their
environment through mechanotransductory processes at focal adhesions, which are
integrin-based contacts connecting the extracellular matrix to the
cytoskeleton. Here we present first steps towards a quantitative understanding
of focal adhesions as mechanosensors. It has been shown experimentally that
high levels of force are related to growth of and signaling at focal adhesions.
In particular, activation of the small GTPase Rho through focal adhesions leads
to the formation of stress fibers. Here we discuss one way in which force might
regulate the internal state of focal adhesions, namely by modulating the
internal rupture dynamics of focal adhesions. A simple two-spring model shows
that the stiffer the environment, the more efficient cellular force is built up
at focal adhesions by molecular motors interacting with the actin filaments.Comment: Latex, 17 pages, 5 postscript figures include
Polaron and Bipolaron Defects in a Charge Density Wave: a Model for Lightly Doped BaBiO3
BaBiO3 is a prototype ``charge ordering system'' forming interpenetrating
sublattices with nominal valence Bi(3+) and Bi(5+). It can also be regarded as
a three-dimensional version of a Peierls insulator, the insulating gap being a
consequence of an ordered distortion of oxygen atoms. When holes are added to
BaBiO3 by doping, it remains insulating until a very large hole concentration
is reached, at which point it becomes superconducting. The mechanism for
insulating behavior of more lightly-doped samples is formation of small
polarons or bipolarons. These are self-organized point defects in the Peierls
order parameter, which trap carriers in bound states inside the Peierls gap. We
calculate properties of the polarons and bipolarons using the Rice-Sneddon
model. Bipolarons are the stable defect; the missing pair of electrons come
from an empty midgap state built from the lower Peierls band. Each bipolaron
distortion also pulls down six localized states below the bottom of the
unoccupied upper Peierls band. The activation energy for bipolaron hopping is
estimated.Comment: 9 pages with 8 embedded figures. See also cond-mat/0108089, a paper
of 5 pages on the related topic of self-trapped excitons in BaBiO
Molecular and cellular factors control signal transduction via switchable allosteric modulator proteins (SAMPs)
Background: Rap proteins from Bacilli directly target response regulators of bacterial two-component systems and modulate their activity. Their effects are controlled by binding of signaling peptides to an allosteric site. Hence Raps exemplify a class of monomeric signaling receptors, which we call switchable allosteric modulator proteins (SAMPs). These proteins have potential applications in diverse biomedical and biotechnical settings, but a quantitative understanding of the impact of molecular and cellular factors on signal transduction is lacking. Here we introduce mathematical models that elucidate how signals are propagated though the network upon receptor stimulation and control the level of active response regulator. Results: Based on a systematic parameter analysis of the models, we show that key features of the dose-response behavior at steady state are controlled either by the molecular properties of the modulator or the signaling context. In particular, we find that the biochemical activity (i.e. non-enzymatic vs. enzymatic) and allosteric properties of the modulator control the response amplitude. The Hill coefficient and the EC50 are controlled in addition by the relative ligand affinities. By tuning receptor properties, either graded or more switch-like (memory-less) response functions can be fashioned. Furthermore, we show that other contextual factors (e.g. relative concentrations of network components and kinase activity) have a substantial impact on the response, and we predict that there exists a modulator concentration which is optimal for response amplitude. Conclusion: We discuss data on Rap-Phr systems in B. subtilis to show how our models can contribute to an integrated view of SAMP signaling by combining biochemical, structural and physiological insights. Our results also suggest that SAMPs could be evolved or engineered to implement diverse response behaviors. However—without additional regulatory controls—they can generate rather variable cellular outputs
Self-Trapped Exciton Defects in a Charge Density Wave: Electronic Excitations of BaBiO3
In the previous paper, it was shown that holes doped into BaBiO3 self-trap as
small polarons and bipolarons. These point defects are energetically favorable
partly because they undo locally the strain in the charge-density-wave (Peierls
insulator) ground state. In this paper the neutral excitations of the same
model are discussed. The lowest electronic excitation is predicted to be a
self-trapped exciton, consisting of an electron and a hole located on adjacent
Bi atoms. This excitation has been seen experimentally (but not identified as
such) via the Urbach tail in optical absorption, and the multi-phonon spectrum
of the ``breathing mode'' seen in Raman scattering. These two phenomena occur
because of the Franck-Condon effect associated with oxygen displacement in the
excited state.Comment: 5 pages with 7 embedded figures. See also cond-mat/0108089 on
polarons and bipolarons in BaBiO3 contains background informatio
Effect of Poisson ratio on cellular structure formation
Mechanically active cells in soft media act as force dipoles. The resulting
elastic interactions are long-ranged and favor the formation of strings. We
show analytically that due to screening, the effective interaction between
strings decays exponentially, with a decay length determined only by geometry.
Both for disordered and ordered arrangements of cells, we predict novel phase
transitions from paraelastic to ferroelastic and anti-ferroelastic phases as a
function of Poisson ratio.Comment: 4 pages, Revtex, 4 Postscript figures include
Cell organization in soft media due to active mechanosensing
Adhering cells actively probe the mechanical properties of their environment
and use the resulting information to position and orient themselves. We show
that a large body of experimental observations can be consistently explained
from one unifying principle, namely that cells strengthen contacts and
cytoskeleton in the direction of large effective stiffness. Using linear
elasticity theory to model the extracellular environment, we calculate optimal
cell organization for several situations of interest and find excellent
agreement with experiments for fibroblasts, both on elastic substrates and in
collagen gels: cells orient in the direction of external tensile strain, they
orient parallel and normal to free and clamped surfaces, respectively, and they
interact elastically to form strings. Our method can be applied for rational
design of tissue equivalents. Moreover our results indicate that the concept of
contact guidance has to be reevaluated. We also suggest that cell-matrix
contacts are upregulated by large effective stiffness in the environment
because in this way, build-up of force is more efficient.Comment: Revtex, 7 pages, 4 Postscript files include
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