Artery and vein formation: a tug of war between different forces.
Ontology highlight
ABSTRACT:
SUBMITTER: Lin FJ
PROVIDER: S-EPMC2002564 | biostudies-other | 2007 Oct
REPOSITORIES: biostudies-other
Similar Datasets
Project description:Symmetric or asymmetric positioning of intracellular structures including the nucleus and mitotic spindle steers various biological processes such as cell migration, division, and embryogenesis. In typical animal cells, both a sparse actomyosin meshwork in the cytoplasm and a dense actomyosin cortex underneath the cell membrane participate in the intracellular positioning. However, it remains unclear how these coexisting actomyosin structures regulate the positioning symmetry. To reveal the potential mechanism, we construct an in vitro model composed of cytoplasmic extracts and nucleus-like clusters confined in droplets. Here we find that periodic centripetal actomyosin waves contract from the droplet boundary push clusters to the center in large droplets, while network percolation of bulk actomyosin pulls clusters to the edge in small droplets. An active gel model quantitatively reproduces molecular perturbation experiments, which reveals that the tug-of-war between two distinct actomyosin networks with different maturation time-scales determines the positioning symmetry.
| S-EPMC7295813 | biostudies-literature
Project description:Synthesizing spatial patterns with genetic networks is an ongoing challenge in synthetic biology. A successful demonstration of pattern formation would imply a better understanding of systems in the natural world and advance applications in synthetic biology. In developmental systems, transient patterning may suffice in order to imprint instructions for long-term development. In this paper we show that transient but persistent patterns can emerge from a realizable synthetic gene network based on a toggle switch. We show that a bistable system incorporating diffusible molecules can generate patterns that resemble Turing patterns but are distinctly different in the underlying mechanism: diffusion of mutually inhibiting molecules creates a prolonged "tug-of-war" between patches of cells at opposing bistable states. The patterns are transient but longer wavelength patterns persist for extended periods of time. Analysis of a representative small scale model implies the eigenvalues of the persistent modes are just above the threshold of stability. The results are verified through simulation of biologically relevant models.
| S-EPMC5693606 | biostudies-literature
Project description:Molecular motor proteins use the energy released from ATP hydrolysis to generate force and haul cargoes along cytoskeletal filaments. Thus, measuring the force motors generate amounts to directly probing their function. We report on optical trapping methodology capable of making precise in vivo stall-force measurements of individual cargoes hauled by molecular motors in their native environment. Despite routine measurement of motor forces in vitro, performing and calibrating such measurements in vivo has been challenging. We describe the methodology recently developed to overcome these difficulties, and used to measure stall forces of both kinesin-1 and cytoplasmic dynein-driven lipid droplets in Drosophila embryos. Critically, by measuring the cargo dynamics in the optical trap, we find that there is memory: it is more likely for a cargo to resume motion in the same direction-rather than reverse direction-after the motors transporting it detach from the microtubule under the force of the optical trap. This suggests that only motors of one polarity are active on the cargo at any instant in time and is not consistent with the tug-of-war models of bidirectional transport where both polarity motors can bind the microtubules at all times. We further use the optical trap to measure in vivo the detachment rates from microtubules of kinesin-1 and dynein-driven lipid droplets. Unlike what is commonly assumed, we find that dynein's but not kinesin's detachment time in vivo increases with opposing load. This suggests that dynein's interaction with microtubules behaves like a catch bond.
| S-EPMC3414874 | biostudies-other
Project description:Membraneless organelles, comprising dozens to hundreds of macromolecular components, form heterogeneous phases in space and evolve over time in material properties. Here, using four macromolecules, we demonstrate a range of phase behaviors associated with membraneless organelles and uncover the underlying physicochemical rules. The macromolecules are SH35 (S) and PRM5 (P), two pentameric, oppositely charged protein constructs; heparin (H), an anionic polymer; and lysozyme (L), a cationic single-domain protein. The S:P, S:L, and P:H binaries form droplets, but the H:L binary forms network-like precipitates, therefore setting up a tug of war between different condensate phases within the S:P:H:L quaternary. The H:L exception can partly be attributed to the compactness of L, as supported by ThT binding data. Increasing amounts of P alone or both S and P, but not S alone, can dissolve H:L precipitates into droplets. These differential effects can be explained by the order of the strengths of pairwise attraction: H:L > P:H > S:P > S:L, deduced from the shapes of ternary phase boundaries. When S and P are at subdissolution concentrations, S:P:H:L precipitates change over time to become droplet-like in appearance, although not completely fluidic according to fluorescence recovery after photobleaching. In fact, confocal microscopy reveals separated S:L-rich and P:H-rich foci inside the droplet-like condensates. Therefore, complex phase behaviors of membraneless organelles, including rescue of aberrant phase transitions, demixing of condensates, and time evolution of material properties, can all be reconstituted and understood via a minimal macromolecular system.
| S-EPMC7323581 | biostudies-literature
Project description:The human immune system is under constant challenge from many viruses, some of which the body is successfully able to clear. Other viruses have evolved to escape the host immune responses and thus persist, leading to the development of chronic diseases. Dendritic cells are professional antigen-presenting cells that play a major role in both innate and adaptive immunity against different pathogens. This review focuses on the interaction of different chronic viruses with dendritic cells and the viruses' ability to exploit this critical cell type to their advantage so as to establish persistence within the host.
| S-EPMC5555304 | biostudies-other
Project description:Glucose-stimulated insulin secretion [GSIS] from the islet β-cell involves a well-orchestrated interplay between metabolic and cationic events. It is well established that intracellular generation of adenine and guanine nucleotide triphosphates [e.g., ATP and GTP] represents one of the requisite signaling steps in GSIS. The small molecular mass GTP-binding proteins [G-proteins; e.g., Rac1 and Cdc42] have been shown to regulate islet β-cell function including actin cytoskeletal remodeling and fusion of insulin granules with the plasma membrane for GSIS to occur. In this context, several regulatory factors for these G-proteins have been identified in the pancreatic β-cell; these include guanine nucleotide exchange factors [GEFs] and guanine nucleotide dissociation inhibitors [GDI]. Recent pharmacological and molecular biological evidence identified Tiam1 and Vav2 as GEFs for Rac1 in promoting physiological insulin secretion. Paradoxically, emerging evidence in multiple cell types, including the islet β-cell, suggests key roles for Rac1 in the onset of cellular dysfunction under conditions of metabolic stress and diabetes. Furthermore, functional inactivation of either Tiam1 or Vav2 appears to attenuate sustained activation of Rac1 and its downstream signaling events [activation of stress kinases] under conditions of metabolic stress. Together, these findings suggest both "friendly" and "non-friendly" roles for Tiam1/Vav2-Rac1 signaling axis in islet β-cell in health and diabetes. Our current understanding of the field and the knowledge gaps that exist in this area of islet biology are heighted herein. Furthermore, potential caveats in the specificity and selectivity of pharmacological inhibitors that are available currently are discussed in this Commentary.
| S-EPMC5382093 | biostudies-literature
Project description:Dynamic and coordinated axonal responses to changing environments are critical for establishing neural connections. As commissural axons migrate across the CNS midline, they are suggested to switch from being attracted to being repelled in order to approach and to subsequently leave the midline. A molecular mechanism that is hypothesized to underlie this switch in axonal responses is the silencing of Netrin1/Deleted in Colorectal Carcinoma (DCC)-mediated attraction by the repulsive SLIT/ROBO1 signaling. Using in vivo approaches including CRISPR-Cas9-engineered mouse models of distinct Dcc splice isoforms, we show here that commissural axons maintain responsiveness to both Netrin and SLIT during midline crossing, although likely at quantitatively different levels. In addition, full-length DCC in collaboration with ROBO3 can antagonize ROBO1 repulsion in vivo. We propose that commissural axons integrate and balance the opposing DCC and Roundabout (ROBO) signaling to ensure proper guidance decisions during midline entry and exit.
| S-EPMC10335249 | biostudies-literature
Project description:Translation is a central cellular process and is optimized for speed and fidelity. The speed of translation of a single codon depends on the concentration of aminoacyl-tRNAs. Here, we used microarray-based approaches to analyze the charging levels of tRNAs in Escherichia coli growing at different growth rates. Strikingly, we observed a non-uniform aminoacylation of tRNAs in complex media. In contrast, in minimal medium, the level of aminoacyl-tRNAs is more uniform and rises to approximately 60%. Particularly, the charging level of tRNA(Ser), tRNA(Cys), tRNA(Thr) and tRNA(His) is below 50% in complex medium and their aminoacylation levels mirror the degree that amino acids inhibit growth when individually added to minimal medium. Serine is among the most toxic amino acids for bacteria and tRNAs(Ser) exhibit the lowest charging levels, below 10%, at high growth rate although intracellular serine concentration is plentiful. As a result some serine codons are among the most slowly translated codons. A large fraction of the serine is most likely degraded by L-serine-deaminase, which competes with the seryl-tRNA-synthetase that charges the tRNAs(Ser) These results indicate that the level of aminoacylation in complex media might be a competition between charging for translation and degradation of amino acids that inhibit growth.
| S-EPMC5041488 | biostudies-literature
Project description:Competition is ubiquitous in microbial communities, shaping both their spatial and temporal structure and composition. Classical minimal models of competition, such as the Moran model, have been employed in ecology and evolutionary biology to understand the role of fixation and invasion in the maintenance of population diversity. Informed by recent experimental studies of cellular competition in confined spaces, we extend the Moran model to incorporate mechanical interactions between cells that divide within the limited space of a one-dimensional open microchannel. The model characterizes the skewed collective growth of the cells dividing within the channel, causing cells to be expelled at the channel ends. The results of this spatial exclusion model differ significantly from those of its classical well-mixed counterpart. The mean time to fixation of a species is greatly accelerated, scaling logarithmically, rather than algebraically, with the system size, and fixation/extinction probability sharply depends on the species' initial fractional abundance. By contrast, successful takeovers by invasive species, whether through mutation or immigration, are substantially less likely than in the Moran model. We also find that the spatial exclusion tends to attenuate the effects of fitness differences on the fixation times and probabilities. We find that these effects arise from the combination of the quasi-neutral "tug-of-war" diffusion dynamics of the inter-species boundary around an unstable equipoise point and the quasi-deterministic avalanche dynamics away from the fixed point. These results, which can be tested in microfluidic monolayer devices, have implications for the maintenance of species diversity in dense bacterial and cellular ecosystems where spatial exclusion is central to the competition, such as in organized biofilms or intestinal crypts.
| S-EPMC10718426 | biostudies-literature
Project description:Cancer progression is an example of a rapid adaptive process where evolving new traits is essential for survival and requires a high mutation rate. Precancerous cells acquire a few key mutations that drive rapid population growth and carcinogenesis. Cancer genomics demonstrates that these few driver mutations occur alongside thousands of random passenger mutations--a natural consequence of cancer's elevated mutation rate. Some passengers are deleterious to cancer cells, yet have been largely ignored in cancer research. In population genetics, however, the accumulation of mildly deleterious mutations has been shown to cause population meltdown. Here we develop a stochastic population model where beneficial drivers engage in a tug-of-war with frequent mildly deleterious passengers. These passengers present a barrier to cancer progression describable by a critical population size, below which most lesions fail to progress, and a critical mutation rate, above which cancers melt down. We find support for this model in cancer age-incidence and cancer genomics data that also allow us to estimate the fitness advantage of drivers and fitness costs of passengers. We identify two regimes of adaptive evolutionary dynamics and use these regimes to understand successes and failures of different treatment strategies. A tumor's load of deleterious passengers can explain previously paradoxical treatment outcomes and suggest that it could potentially serve as a biomarker of response to mutagenic therapies. The collective deleterious effect of passengers is currently an unexploited therapeutic target. We discuss how their effects might be exacerbated by current and future therapies.
| S-EPMC4210325 | biostudies-literature