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The true slime mold Physarum polycephalum exhibits a vast array of sophisticated manipulations of its intracellular cytoplasm. Growing microplasmodia of Physarum have been observed to adopt an elongated tadpole shape, then contract in a rhythmic, traveling wave pattern that resembles peristaltic pumping. This contraction drives a fast flow of non-gelated cytoplasm along the cell longitudinal axis. It has been hypothesized that this flow of cytoplasm is a driving factor in generating motility of the plasmodium. In this work, we use two different mathematical models to investigate how peristaltic pumping within Physarum may be used to drive cellular motility. We compare the relative phase of flow and deformation waves predicted by both models to similar phase data collected from in vivo experiments using Physarum plasmodia. The first is a PDE model based on a dimensional reduction of peristaltic pumping within a finite length chamber. The second is a more sophisticated computational model which accounts for more general shape changes, more complex cellular mechanics, and dynamically modulated adhesion to the underlying substrate. This model allows us to directly compute cell crawling speed. Both models suggest that a mechanical asymmetry in the cell is required to reproduce the experimental observations. Such a mechanical asymmetry is also shown to increase the potential for cellular migration, as measured by both stress generation and migration velocity.

This work examines the relationship between spatio-temporal coordination of intracellular flow and traction stress and the speed of amoeboid locomotion of microplasmodia of Physarum polycephalum. We simultaneously perform particle image velocimetry and traction stress microscopy to measure the velocity of cytoplasmic flow and the stresses applied to the substrate by migrating Physarum microamoebae. In parallel, we develop a mathematical model of a motile cell which includes forces from the viscous cytosol, a poro-elastic, contractile cytoskeleton and adhesive interactions with the substrate. Our experiments show that flow and traction stress exhibit back-to-front-directed waves with a distinct phase difference. The model demonstrates that the direction and speed of locomotion are determined by this coordination between contraction, flow and adhesion. Using the model, we identify forms of coordination that generate model predictions consistent with experiments. We demonstrate that this coordination produces near optimal migration speed and is insensitive to heterogeneity in substrate adhesiveness. While it is generally thought that amoeboid motility is robust to changes in extracellular geometry and the nature of extracellular adhesion, our results demonstrate that coordination of adhesive forces is essential to producing robust migration.

F-actin networks are involved in cell mechanical processes ranging from motility to endocytosis. The mesoscale architecture of assemblies of individual F-actin polymers that gives rise to micrometer-scale rheological properties is poorly understood, despite numerous in vivo and vitro studies. In vitro networks have been shown to organize into spatial patterns when spatially confined, including dense spherical shells inside spherical emulsion droplets. Here we develop a simplified model of an isotropic, compressible, viscoelastic material continually assembling and disassembling. We demonstrate that spherical shells emerge naturally when the strain relaxation rate (corresponding to internal network reorganization) is slower than the disassembly rate (corresponding to F-actin depolymerization). These patterns are consistent with recent experiments, including a collapse of shells to a central high-density focus of F-actin when either assembly or disassembly is reduced with drugs. Our results demonstrate how complex spatio-temporal patterns can emerge without spatially distributed force generation, polar alignment of F-actin polymers, or spatially nonuniform regulation of F-actin by upstream biochemical networks.

Mast cells and IgE are most familiar as the effectors of type I hypersensitivity reactions including anaphylaxis. It is becoming clear however that this pair has important immunomodulatory effects on innate and adaptive cells of the immune system. In this purview, they act as endogenous adjuvants to ignite evolving immune responses, promote the transition of allergic disease into chronic illness and disrupt the development of active mechanisms of tolerance to ingested foods. Suppression of IgE-mediated mast cell activation can be exerted by molecules targeting IgE, FcɛRI or signaling kinases including Syk, or by IgG antibodies acting via inhibitory Fcγ receptors. In 2015 we reviewed the evidence for the adjuvant functions of mast cells. This update includes the original text, incorporates some important developments in the field over the past five years and discusses how interventions targeting these pathways might have promise in the development of strategies to treat allergic disease. [ABSTRACT FROM AUTHOR]

Gastric mucus gel is known to exhibit dramatic and unique swelling behaviors in response to the ionic composition of the hydrating solution. This swelling behavior is important in the maintenance of the mucus layer lining the stomach wall, as the layer is constantly digested by enzymes in the lumen, and must be replenished by new mucus that swells as it is secreted from the gastric wall. One hypothesis suggests that the condensed state of mucus at secretion is maintained by transient bonds with calcium that form crosslinks. These crosslinks are lost as monovalent cations from the environment displace divalent crosslinkers, leading to a dramatic change in the energy of the gel and inducing the swelling behavior. Previous modeling work has characterized the equilibrium behavior of polyelectrolyte gels that respond to calcium crosslinking. Here, we present an investigation of the dynamic swelling behavior of a polyelectrolytic gel model of mucus. In particular, we quantified the rate at which a globule of initially crosslinked gel swells when exposed to an ionic bath. The dependence of this swelling rate on several parameters was characterized. We observed that swelling rate has a non-monotone dependence on the molarity of the bath solution, with moderate concentrations of available sodium inducing the fastest swelling.

It is generally accepted that the gastric mucus layer provides a protective barrier between the lumen and the mucosa, shielding the mucosa from acid and digestive enzymes and preventing autodigestion of the stomach epithelium. However, the precise mechanisms that contribute to this protective function are still up for debate. In particular, it is not clear what physical processes are responsible for transporting hydrogen protons, secreted within the gastric pits, across the mucus layer to the lumen without acidifying the environment adjacent to the epithelium. One hypothesis is that hydrogen may be bound to the mucin polymers themselves as they are convected away from the mucosal surface and eventually degraded in the stomach lumen. It is also not clear what mechanisms prevent hydrogen from diffusing back toward the mucosal surface, thereby lowering the local pH. In this work we investigate a physics-based model of ion transport within the mucosal layer based on a Nernst-Planck-like equation. Analysis of this model shows that the mechanism of transporting protons bound to the mucus gel is capable of reproducing the trans-mucus pH gradients reported in the literature. Furthermore, when coupled with ion exchange at the epithelial surface, our analysis shows that bicarbonate secretion alone is capable of neutralizing the epithelial pH, even in the face of enormous diffusive gradients of hydrogen. Maintenance of the pH gradient is found to be robust to a wide array of perturbations in both physiological and phenomenological model parameters, suggesting a robust physiological control mechanism. NEW & NOTEWORTHY This work combines modeling techniques based on physical principles, as well as novel numerical simulations to test the plausibility of one hypothesized mechanism for proton transport across the gastric mucus layer. Results show that this mechanism is able to maintain the extreme pH gradient seen in in vivo experiments and suggests a highly robust regulation mechanism to maintain this gradient in the face of dynamic lumen composition., (Copyright © 2017 the American Physiological Society.)