34,355 research outputs found
Universal features of cell polarization processes
Cell polarization plays a central role in the development of complex
organisms. It has been recently shown that cell polarization may follow from
the proximity to a phase separation instability in a bistable network of
chemical reactions. An example which has been thoroughly studied is the
formation of signaling domains during eukaryotic chemotaxis. In this case, the
process of domain growth may be described by the use of a constrained
time-dependent Landau-Ginzburg equation, admitting scale-invariant solutions
{\textit{\`a la}} Lifshitz and Slyozov. The constraint results here from a
mechanism of fast cycling of molecules between a cytosolic, inactive state and
a membrane-bound, active state, which dynamically tunes the chemical potential
for membrane binding to a value corresponding to the coexistence of different
phases on the cell membrane. We provide here a universal description of this
process both in the presence and absence of a gradient in the external
activation field. Universal power laws are derived for the time needed for the
cell to polarize in a chemotactic gradient, and for the value of the smallest
detectable gradient. We also describe a concrete realization of our scheme
based on the analysis of available biochemical and biophysical data.Comment: Submitted to Journal of Statistical Mechanics -Theory and Experiment
Coupling of cytoplasm and adhesion dynamics determines cell polarization and locomotion
Observations of single epidermal cells on flat adhesive substrates have
revealed two distinct morphological and functional states, namely a
non-migrating symmetric unpolarized state and a migrating asymmetric polarized
state. These states are characterized by different spatial distributions and
dynamics of important biochemical cell components: F-actin and myosin-II form
the contractile part of the cytoskeleton, and integrin receptors in the plasma
membrane connect F-actin filaments to the substratum. In this way, focal
adhesion complexes are assembled, which determine cytoskeletal force
transduction and subsequent cell locomotion. So far, physical models have
reduced this phenomenon either to gradients in regulatory control molecules or
to different mechanics of the actin filament system in different regions of the
cell.
Here we offer an alternative and self-organizational model incorporating
polymerization, pushing and sliding of filaments, as well as formation of
adhesion sites and their force dependent kinetics. All these phenomena can be
combined into a non-linearly coupled system of hyperbolic, parabolic and
elliptic differential equations. Aim of this article is to show how relatively
simple relations for the small-scale mechanics and kinetics of participating
molecules may reproduce the emergent behavior of polarization and migration on
the large-scale cell level.Comment: v2 (updates from proof): add TOC, clarify Fig. 4, fix several typo
Droplet Ripening in Concentration Gradients
Living cells use phase separation and concentration gradients to organize
chemical compartments in space. Here, we present a theoretical study of droplet
dynamics in gradient systems. We derive the corresponding growth law of
droplets and find that droplets exhibit a drift velocity and position dependent
growth. As a consequence, the dissolution boundary moves through the system,
thereby segregating droplets to one end. We show that for steep enough
gradients, the ripening leads to a transient arrest of droplet growth that is
induced by an narrowing of the droplet size distribution.Comment: 12 pages, 4 figure
Generation and escape of local waves from the boundary of uncoupled cardiac tissue
We aim to understand the formation of abnormal waves of activity from
myocardial regions with diminished cell-to-cell coupling. In route to this
goal, we studied the behavior of a heterogeneous myocyte network in which a
sharp coupling gradient was placed under conditions of increasing network
automaticity. Experiments were conducted in monolayers of neonatal rat
cardiomyocytes using heptanol and isoproterenol as means of altering
cell-to-cell coupling and automaticity respectively. Experimental findings were
explained and expanded using a modified Beeler-Reuter numerical model. The data
suggests that the combination of a heterogeneous substrate, a gradient of
coupling and an increase in oscillatory activity of individual cells creates a
rich set of behaviors associated with self-generated spiral waves and ectopic
sources. Spiral waves feature a flattened shape and a pin-unpin drift type of
tip motion. These intercellular waves are action-potential based and can be
visualized with either voltage or calcium transient measurements. A source/load
mismatch on the interface between the boundary and well-coupled layers can lock
wavefronts emanating from both ectopic sources and rotating waves within the
inner layers of the coupling gradient. A numerical approach allowed us to
explore how: i) the spatial distribution of cells, ii) the amplitude and
dispersion of cell automaticity, iii) and the speed at which the coupling
gradient moves in space, affects wave behavior, including its escape into
well-coupled tissue.Comment: 28 pages, 10 figures, submitted to Biophysical Journa
Interplay of packing and flip-flop in local bilayer deformation. How phosphatidylglycerol could rescue mitochondrial function in a cardiolipin-deficient yeast mutant
In a previous work, we have shown that a spatially localized transmembrane pH
gradient, produced by acid micro-injection near the external side of
cardiolipin-containing giant unilamellar vesicles, leads to the formation of
tubules that retract after the dissipation of this gradient. These tubules have
morphologies similar to mitochondrial cristae. The tubulation effect is due to
direct phospholipid packing modification in the outer leaflet that is promoted
by protonation of cardiolipin headgroups. Here we compare the case of
cardiolipin-containing giant unilamellar vesicles with that of
phosphatidylglycerol-containing giant unilamellar vesicles. Local acidification
also promotes formation of tubules in the latter. However, compared to
cardiolipin-containing giant unilamellar vesicles the tubules are longer,
exhibit a visible pearling and have a much longer lifetime after acid
micro-injection is stopped. We attribute these differences to an additional
mechanism that increases monolayer surface imbalance, namely inward PG
flip-flop promoted by the local transmembrane pH-gradient. Simulations using a
fully non-linear membrane model as well as geometrical calculations are in
agreement with this hypothesis. Interestingly, among yeast mutants deficient in
cardiolipin biosynthesis, only the crd1-null mutant, which accumulates
phosphatidylglycerol, displays significant mitochondrial activity. Our work
provides a possible explanation of such a property and further emphasizes the
salient role of specific lipids in mitochondrial function.Comment: 28 pages, 10 figure
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