314,637 research outputs found
Dynamic Image-Based Modelling of Kidney Branching Morphogenesis
Kidney branching morphogenesis has been studied extensively, but the
mechanism that defines the branch points is still elusive. Here we obtained a
2D movie of kidney branching morphogenesis in culture to test different models
of branching morphogenesis with physiological growth dynamics. We carried out
image segmentation and calculated the displacement fields between the frames.
The models were subsequently solved on the 2D domain, that was extracted from
the movie. We find that Turing patterns are sensitive to the initial conditions
when solved on the epithelial shapes. A previously proposed diffusion-dependent
geometry effect allowed us to reproduce the growth fields reasonably well, both
for an inhibitor of branching that was produced in the epithelium, and for an
inducer of branching that was produced in the mesenchyme. The latter could be
represented by Glial-derived neurotrophic factor (GDNF), which is expressed in
the mesenchyme and induces outgrowth of ureteric branches. Considering that the
Turing model represents the interaction between the GDNF and its receptor RET
very well and that the model reproduces the relevant expression patterns in
developing wildtype and mutant kidneys, it is well possible that a combination
of the Turing mechanism and the geometry effect control branching
morphogenesis
Spots & stripes: pleomorphic patterning of stem cells via p-ERK-depenendent cell chemotaxis shown by feather morphogenesis & mathematical simulation
A key issue in stem cell biology is the differentiation of homogeneous stem cells towards different fates which are also organized into desired configurations. Little is known about the mechanisms underlying the process of periodic patterning. Feather explants offer a fundamental and testable model in which multi-potential cells are organized into hexagonally arranged primordia and the spacing between primordia. Previous work explored roles of a Turing reaction–diffusion mechanism in establishing chemical patterns. Here we show that a continuum of feather patterns, ranging from stripes to spots, can be obtained when the level of p-ERK activity is adjusted with chemical inhibitors. The patterns are dose-dependent, tissue stage-dependent, and irreversible. Analyses show that ERK activity-dependent mesenchymal cell chemotaxis is essential for converting micro-signaling centers into stable feather primordia. A mathematical model based on short-range activation, long-range inhibition, and cell chemotaxis is developed and shown to simulate observed experimental results. This generic cell behavior model can be applied to model stem cell patterning behavior at large
Bistability: Requirements on Cell-Volume, Protein Diffusion, and Thermodynamics
Bistability is considered wide-spread among bacteria and eukaryotic cells,
useful e.g. for enzyme induction, bet hedging, and epigenetic switching.
However, this phenomenon has mostly been described with deterministic dynamic
or well-mixed stochastic models. Here, we map known biological bistable systems
onto the well-characterized biochemical Schloegl model, using analytical
calculations and stochastic spatio-temporal simulations. In addition to network
architecture and strong thermodynamic driving away from equilibrium, we show
that bistability requires fine-tuning towards small cell volumes (or
compartments) and fast protein diffusion (well mixing). Bistability is thus
fragile and hence may be restricted to small bacteria and eukaryotic nuclei,
with switching triggered by volume changes during the cell cycle. For large
volumes, single cells generally loose their ability for bistable switching and
instead undergo a first-order phase transition.Comment: 23 pages, 8 figure
Oxygen diffusion and reactivity at low temperature on bare amorphous olivine-type silicate
The mobility of O atoms at very low temperatures is not generally taken into
account, despite O diffusion would add to a series of processes leading to the
observed rich molecular diversity in space. We present a study of the mobility
and reactivity of O atoms on an amorphous silicate surface. Our results are in
the form of RAIRS and temperature-programmed desorption spectra of O2 and O3
produced via two pathways: O + O and O2 + O, investigated in a submonolayer
regime and in the range of temperature between 6.5 and 30 K. All the
experiments show that ozone is formed efficiently on silicate at any surface
temperature between 6.5 and 30 K. The derived upper limit for the activation
barriers of O + O and O2 + O reactions is 150 K/kb. Ozone formation at low
temperatures indicates that fast diffusion of O atoms is at play even at 6.5 K.
Through a series of rate equations included in our model, we also address the
reaction mechanisms and show that neither the Eley Rideal nor the Hot atom
mechanisms alone can explain the experimental values. The rate of diffusion of
O atoms, based on modeling results, is much higher than the one generally
expected, and the diffusive process proceeds via the Langmuir-Hinshelwood
mechanism enhanced by tunnelling. In fact, quantum effects turn out to be a key
factor that cannot be neglected in our simulations. Astrophysically, efficient
O3 formation on interstellar dust grains would imply the presence of huge
reservoirs of oxygen atoms. Since O3 is a reservoir of elementary oxygen, and
also of OH via its hydrogenation, it could explain the observed concomitance of
CO2 and H2O in the ices.Comment: 28 pages, 14 figure
Differential cargo mobilisation within Weibel-Palade bodies after transient fusion with the plasma membrane.
Inflammatory chemokines can be selectively released from Weibel-Palade bodies (WPBs) during kiss-and-run exocytosis. Such selectivity may arise from molecular size filtering by the fusion pore, however differential intra-WPB cargo re-mobilisation following fusion-induced structural changes within the WPB may also contribute to this process. To determine whether WPB cargo molecules are differentially re-mobilised, we applied FRAP to residual post-fusion WPB structures formed after transient exocytosis in which some or all of the fluorescent cargo was retained. Transient fusion resulted in WPB collapse from a rod to a spheroid shape accompanied by substantial swelling (>2 times by surface area) and membrane mixing between the WPB and plasma membranes. Post-fusion WPBs supported cumulative WPB exocytosis. To quantify diffusion inside rounded organelles we developed a method of FRAP analysis based on image moments. FRAP analysis showed that von Willebrand factor-EGFP (VWF-EGFP) and the VWF-propolypeptide-EGFP (Pro-EGFP) were immobile in post-fusion WPBs. Because Eotaxin-3-EGFP and ssEGFP (small soluble cargo proteins) were largely depleted from post-fusion WPBs, we studied these molecules in cells preincubated in the weak base NH4Cl which caused WPB alkalinisation and rounding similar to that produced by plasma membrane fusion. In these cells we found a dramatic increase in mobilities of Eotaxin-3-EGFP and ssEGFP that exceeded the resolution of our method (∼ 2.4 µm2/s mean). In contrast, the membrane mobilities of EGFP-CD63 and EGFP-Rab27A in post-fusion WPBs were unchanged, while P-selectin-EGFP acquired mobility. Our data suggest that selective re-mobilisation of chemokines during transient fusion contributes to selective chemokine secretion during transient WPB exocytosis. Selective secretion provides a mechanism to regulate intravascular inflammatory processes with reduced risk of thrombosis
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