Cell contact, movement and directionality are important factors in biological development (morphogenesis), and myxobacteria are a model system for studying cell-cell interaction and cell organization ...preceding differentiation. When starved, thousands of myxobacteria cells align, stream and form aggregates which later develop into round, non-motile spores. Canonically, cell aggregation has been attributed to attractive chemotaxis, a long range interaction, but there is growing evidence that myxobacteria organization depends on contact-mediated cell-cell communication. We present a discrete stochastic model based on contact-mediated signaling that suggests an explanation for the initialization of early aggregates, aggregation dynamics and final aggregate distribution. Our model qualitatively reproduces the unique structures of myxobacteria aggregates and detailed stages which occur during myxobacteria aggregation: first, aggregates initialize in random positions and cells join aggregates by random walk; second, cells redistribute by moving within transient streams connecting aggregates. Streams play a critical role in final aggregate size distribution by redistributing cells among fewer, larger aggregates. The mechanism by which streams redistribute cells depends on aggregate sizes and is enhanced by noise. Our model predicts that with increased internal noise, more streams would form and streams would last longer. Simulation results suggest a series of new experiments.
During vertebrate gastrulation, convergence and extension (C&E) movements narrow and lengthen the embryonic tissues, respectively. In zebrafish, regional differences of C&E movements have been ...observed; however, the underlying cell behaviors are poorly understood. Using time-lapse analyses and computational modeling, we demonstrate that C&E of the medial presomitic mesoderm is achieved by cooperation of planar and radial cell intercalations. Radial intercalations preferentially separate anterior and posterior neighbors to promote extension. In knypek;trilobite noncanonical Wnt mutants, the frequencies of cell intercalations are altered and the anteroposterior bias of radial intercalations is lost. This provides evidence for noncanonical Wnt signaling polarizing cell movements between different mesodermal cell layers. We further show using fluorescent fusion proteins that during dorsal mesoderm C&E, the noncanonical Wnt component Prickle localizes at the anterior cell edge, whereas Dishevelled is enriched posteriorly. Asymmetrical localization of Prickle and Dishevelled to the opposite cell edges in zebrafish gastrula parallels their distribution in fly, and suggests that noncanonical Wnt signaling defines distinct anterior and posterior cell properties to bias cell intercalations.
Proteoliposome reconstitution is a standard method to stabilize purified transmembrane proteins in membranes for structural and functional assays. Here we quantified intrareconstitution ...heterogeneities in single proteoliposomes using fluorescence microscopy. Our results suggest that compositional heterogeneities can severely skew ensemble-average proteoliposome measurements but also enable ultraminiaturized high-content screens. We took advantage of this screening capability to map the oligomerization energy of the β2-adrenergic receptor using ∼10(9)-fold less protein than conventional assays.
\({\bf Background:}\) The early growth dynamics of the West African Ebola virus epidemic has been qualitatively different for Guinea, Sierra Leone and Liberia. However, it is important to understand ...these disparate dynamics as trends of a single epidemic spread over regions with similar geographic and cultural aspects, with likely common parameters for transmission rates and the reproduction number \(R_0\). \({\bf Methods:}\) We combine a discrete, stochastic SEIR model with a two-scale community network model to demonstrate that the different regional trends may be explained by different community mixing rates. Heuristically, the effect of different community mixing rates may be understood as the observation that two individuals infected by the same chain of transmission are more likely to know one another in a less-mixed community. Saturation effects occur as the contacts of an infected individual are more likely to already be exposed by the same chain of transmission. \({\bf Results:}\) The effects of community mixing, together with the effects of stochasticity, can explain the qualitative difference in the growth of Ebola virus cases in each country, and why the probability of large outbreaks may have recently increased. An increase in the rate of Ebola cases in Guinea in late August, and a local fitting of the transient dynamics of the Ebola cases in Liberia, suggests that the epidemic in Liberia has been more severe, and the epidemic in Guinea is worsening, due to discrete seeding events as the epidemic spreads into new communities. \({\bf Conclusions:}\) A relatively simple network model provides insight on the role of local effects such as saturation that would be difficult to otherwise quantify. Our results predict that exponential growth of an epidemic is driven by the exposure of new communities, underscoring the importance of control measures that limit this spread.
A lattice-gas cellular automaton (LGCA) model is used to simulate rippling
and aggregation in myxobacteria. An efficient way of representing cells of
different cell size, shape and orientation is ...presented that may be easily
extended to model later stages of fruiting body formation. This LGCA model is
designed to investigate whether a refractory period, a minimum response time, a
maximum oscillation period and non-linear dependence of reversals of cells on
C-factor are necessary assumptions for rippling. It is shown that a refractory
period of 2-3 minutes, a minimum response time of up to 1 minute and no maximum
oscillation period best reproduce rippling in the experiments of {\it
Myxoccoccus xanthus}. Non-linear dependence of reversals on C-factor is
critical at high cell density. Quantitative simulations demonstrate that the
increase in wavelength of ripples when a culture is diluted with non-signaling
cells can be explained entirely by the decreased density of C-signaling cells.
This result further supports the hypothesis that levels of C-signaling
quantitatively depend on and modulate cell density. Analysis of the
interpenetrating high density waves shows the presence of a phase shift
analogous to the phase shift of interpenetrating solitons. Finally, a model for
swarming, aggregation and early fruiting body formation is presented.
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