171 research outputs found
Impact of global structure on diffusive exploration of organelle networks
We investigate diffusive search on planar networks, motivated by tubular
organelle networks in cell biology that contain molecules searching for
reaction partners and binding sites. Exact calculation of the diffusive mean
first-passage time on a spatial network is used to characterize the typical
search time as a function of network connectivity. We find that global
structural properties --- the total edge length and number of loops --- are
sufficient to largely determine network exploration times for a variety of both
synthetic planar networks and organelle morphologies extracted from living
cells. For synthetic networks on a lattice, we predict the search time
dependence on these global structural parameters by connecting with percolation
theory, providing a bridge from irregular real-world networks to a simpler
physical model. The dependence of search time on global network structural
properties suggests that network architecture can be designed for efficient
search without controlling the precise arrangement of connections.
Specifically, increasing the number of loops substantially decreases search
times, pointing to a potential physical mechanism for regulating reaction rates
within organelle network structures.Comment: 13 pages, 4 figures. Accepted for publication in Scientific Report
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Cytoplasmic Flow and Mixing Due to Deformation of Motile Cells.
The cytoplasm of a living cell is a dynamic environment through which intracellular components must move and mix. In motile, rapidly deforming cells such as human neutrophils, bulk cytoplasmic flow couples cell deformation to the transport and dispersion of cytoplasmic particles. Using particle-tracking measurements in live neutrophil-like cells, we demonstrate that fluid flow associated with the cell deformation contributes to the motion of small acidic organelles, dominating over diffusion on timescales above a few seconds. We then use a general physical model of particle dispersion in a deforming fluid domain to show that transport of organelle-sized particles between the cell periphery and the bulk can be enhanced by dynamic deformation comparable to that observed in neutrophils. Our results implicate an important mechanism contributing to organelle transport in these motile cells: cytoplasmic flow driven by cell shape deformation
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Listeria monocytogenes cell-to-cell spread in epithelia is heterogeneous and dominated by rare pioneer bacteria.
Listeria monocytogenes hijacks host actin to promote its intracellular motility and intercellular spread. While L. monocytogenes virulence hinges on cell-to-cell spread, little is known about the dynamics of bacterial spread in epithelia at a population level. Here, we use live microscopy and statistical modeling to demonstrate that L. monocytogenes cell-to-cell spread proceeds anisotropically in an epithelial monolayer in culture. We show that boundaries of infection foci are irregular and dominated by rare pioneer bacteria that spread farther than the rest. We extend our quantitative model for bacterial spread to show that heterogeneous spreading behavior can improve the chances of creating a persistent L. monocytogenes infection in an actively extruding epithelium. Thus, our results indicate that L. monocytogenes cell-to-cell spread is heterogeneous, and that rare pioneer bacteria determine the frontier of infection foci and may promote bacterial infection persistence in dynamic epithelia. Editorial note:This article has been through an editorial process in which the authors decide how to respond to the issues raised during peer review. The Reviewing Editor's assessment is that all the issues have been addressed (see decision letter)
Design principles for the glycoprotein quality control pathway
Newly-translated glycoproteins in the endoplasmic reticulum (ER) often
undergo cycles of chaperone binding and release in order to assist in folding.
Quality control is required to distinguish between proteins that have completed
native folding, those that have yet to fold, and those that have misfolded.
Using quantitative modeling, we explore how the design of the quality-control
pathway modulates its efficiency. Our results show that an energy-consuming
cyclic quality-control process, similar to the observed physiological system,
outperforms alternative designs. The kinetic parameters that optimize the
performance of this system drastically change with protein production levels,
while remaining relatively insensitive to the protein folding rate. Adjusting
only the degradation rate, while fixing other parameters, allows the pathway to
adapt across a range of protein production levels, aligning with in vivo
measurements that implicate the release of degradation-associated enzymes as a
rapid-response system for perturbations in protein homeostasis. The
quantitative models developed here elucidate design principles for effective
glycoprotein quality control in the ER, improving our mechanistic understanding
of a system crucial to maintaining cellular health.Comment: 22 pages, 8 figure
Drive, filter, and stick: A protein sorting conspiracy in photoreceptors.
The sorting of proteins into different functional compartments is a fundamental cellular task. In this issue, Maza et al. (2019. J. Cell Biol https://doi.org/10.1083/jcb.201906024) demonstrate that distinct protein populations are dynamically generated in specialized regions of photoreceptors via an interplay of protein-membrane affinity, impeded diffusion, and driven transport
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Laboratory Simulations of Suprauroral Mechanisms Leading to Perpendicular Ion Heating and Conic Formation
Laboratory experiments are presented simulating aspects of perpendicular ion heating and conic formation that are observed or hypothesized to occur in the terrestrial ionosphere and magnetosphere. Previous laboratory observations of ion conics in the presence of the currentâdriven electrostatic ion cyclotron wave are reviewed. Fieldâaligned ion beams, accompanied by beamâgenerated electrostatic ion cyclotron modes, resulted in perpendicular energization of beam ions and also the heating of background plasma ions. Antennaâlaunched broadband and narrowâband lower hybrid waves produced considerable perpendicular ion heating and nonâMaxwellian âtailâ formation. Laboratory results are discussed in light of in situ measurements by the S3â3 satellite and the MARIE sounding rocket
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High-resolution and high-accuracy topographic and transcriptional maps of the nucleosome barrier.
Nucleosomes represent mechanical and energetic barriers that RNA Polymerase II (Pol II) must overcome during transcription. A high-resolution description of the barrier topography, its modulation by epigenetic modifications, and their effects on Pol II nucleosome crossing dynamics, is still missing. Here, we obtain topographic and transcriptional (Pol II residence time) maps of canonical, H2A.Z, and monoubiquitinated H2B (uH2B) nucleosomes at near base-pair resolution and accuracy. Pol II crossing dynamics are complex, displaying pauses at specific loci, backtracking, and nucleosome hopping between wrapped states. While H2A.Z widens the barrier, uH2B heightens it, and both modifications greatly lengthen Pol II crossing time. Using the dwell times of Pol II at each nucleosomal position we extract the energetics of the barrier. The orthogonal barrier modifications of H2A.Z and uH2B, and their effects on Pol II dynamics rationalize their observed enrichment in +1 nucleosomes and suggest a mechanism for selective control of gene expression
Regulation of Lifespan in Drosophila by Modulation of Genes in the TOR Signaling Pathway
In many species, reducing nutrient intake without causing malnutrition extends lifespan 1, 2, 3. Like DR (dietary restriction), modulation of genes in the insulin-signaling pathway, known to alter nutrient sensing, has been shown to extend lifespan in various species 1, 2, 3, 4. In Drosophila, the target of rapamycin (TOR) and the insulin pathways have emerged as major regulators of growth and size. Hence we examined the role of TOR pathway genes in regulating lifespan by using Drosophila. We show that inhibition of TOR signaling pathway by alteration of the expression of genes in this nutrient-sensing pathway, which is conserved from yeast to human, extends lifespan in a manner that may overlap with known effects of dietary restriction on longevity. In Drosophila, TSC1 and TSC2 (tuberous sclerosis complex genes 1 and 2) act together to inhibit TOR (target of rapamycin), which mediates a signaling pathway that couples amino acid availability to S6 kinase, translation initiation, and growth [5]. We find that overexpression of dTsc1, dTsc2, or dominant-negative forms of dTOR or dS6K all cause lifespan extension. Modulation of expression in the fat is sufficient for the lifespan-extension effects. The lifespan extensions are dependent on nutritional condition, suggesting a possible link between the TOR pathway and dietary restriction
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