True Slime Mold Research Articles

Network emergence and reorganization in confined slime moulds

A fundamental question regarding biological transport networks is the interplay between the network development or reorganization and the flows it carries. We use Physarum polycephalum, a true slime mould with a transport network which adapts quickly to change of external conditions, as a biological model to make progress in this question. We explore the network formation and reorganization in samples suddenly confined in chambers with ring geometry. Using an image analysis method based on the structure tensor, we quantify the emergence and directionality of the network. We show that confinement induces a reorganization of the network with a typical 104 s timescale, during which veins align circumferentially along the ring. We show that this network evolution relies on local dynamics.

Interview with FocalPlane Scientific Advisory Board member Kota Miura

ABSTRACT Kota Miura is the Vice-Chair of the Network of European Bioimage Analysts (NEUBIAS) and a freelance bioimage analyst. For his PhD, Kota studied cell migration in true and cellular slime molds where he was introduced to bioimage analysis, which became the focus of his research. After moving to EMBL at Heidelberg in Germany, Kota was instrumental in running the EMBL bioimages analysis courses and in founding NEUBIAS. We caught up with Kota to discuss his career, his hopes for the future of bioimage analysis and how FocalPlane can benefit the microscopy community.

Relation between learning process and morphology of transport tube network in plasmodium of Physarum polycephalum.

The question of whether a single-celled organism without a brain could have functions such as learning and memory has been the subject of much debate in recent years. The plasmodium of the true slime mold, Physarum polycephalum, is an ideal model organism for such a question. The plasmodium exhibits behaviors that resemble intelligence, including solving mazes, mimicking optimal rail transportation networks, predicting the weather, and solving traveling salesman problems. In addition, the plasmodium has recently been shown to have the simplest form of learning: habituation. In the experiments in which plasmodia were repeatedly allowed to cross bridges containing aversive chemicals, the habituation behavior has been confirmed. It has been shown that the habituation process involves chemicals that are stored internally. However, it is not clear how these chemicals result in change in the behavior of plasmodium during habituation learning. This study focused on the transport tube network formed in plasmodium during the above experiments. Then, the role of the network morphology in the habituation learning process was investigated. The results showed that the network morphology changes from tree to mesh type during habituation learning, and disrupting the learned network reduces habituation behavior. In addition, it was shown that the thickness oscillation frequency depends on the network morphology. The study found that in the plasmodium of P. polycephalum, a primitive organism without a brain, transport tube networks, instead of neuronal networks, play an important role in habituation learning and the resulting decision making.

Analysis of the trehalose synthesis pathway of Physarum polycehalum

Desiccation is a severe survival problem for organisms. We have been studying the desiccation tolerance mechanisms in the true slime mold Physarum polycephalum. We measured the trehalose content of P. polycephalum vegetative cells (plasmodia) and drought cells (sclerotia). Surprisingly, we found that the content in sclerotia was about 473-fold greater than in the plasmodia. We then examined trehalose metabolism-related genes via RNAseq, and consequently found that trehalose 6-phosphate phosphorylase (T6pp) expression levels increased following desiccation. Next, we cloned and expressed the genes for T6pp, trehalose 6-phosphate synthase/phosphatase (Tps/Tpp), maltooligosyltrehalose trehalohydrolase (TreZ), and maltooligosyltrehalose synthase (TreY) in E. coli. Incidentally, TreY and TreZ clones have been reported in several prokaryotes, but not in eukaryotes. This report in P. polycephalum is the first evidence of their presence in a eukaryote species. Recombinant T6pp, TreY, and TreZ were purified and confirmed to be active. Our results showed that these enzymes catalyze reactions related to trehalose production, and their reaction kinetics follow the Michaelis-Menten equation.The t6pp mRNA levels of the sclerotia were about 15-fold higher than in the plasmodia. In contrast, the expression levels of TreZ and TreY showed no significant change between the sclerotia and plasmodia. Thus, T6pp is probably related to desiccation tolerance, whereas the contribution of TreY and TreZ is insufficient to account for the considerable accumulation of trehalose in sclerotia.

Two-carba cyclic phosphatidic acid treatment promotes phenotypic switch from M1 to M2 microglia and prevents behavioral abnormalities in a mouse model of neuropsychiatric systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is an autoimmune disease associated with the production of double-stranded DNA (dsDNA) antibodies and other antibodies that predominantly affects women with a wide range of lesions. Although neuropsychiatric lupus erythematosus (NPSLE), characterized by neuropsychiatric symptoms related to cerebrovascular diseases or depression, ranks high in severity, no specific treatment has been defined. Two-carba cyclic phosphatidic acid (2ccPA), a derivative of cyclic phosphatidic acid, was isolated from the true slime mold Physarum polycephalum in 1992. 2ccPA treatment suppresses neuroinflammation and promotes tissue repair in mouse multiple sclerosis and traumatic brain injury models. In this study, we performed behavioral tests on MRL/lpr mice as an NPSLE model. MRL/lpr mice showed increased depression-like behaviors compared with control mice, which were significantly suppressed by 2ccPA treatment. The expression of CD68, an M1 phenotypic marker of microglia, was significantly elevated in the prefrontal cortex and hippocampus of MRL/lpr mice, which was significantly suppressed by 2ccPA treatment. In contrast, the expression of Arginase1, an M2 phenotypic marker of microglia, was significantly increased by 2ccPA treatment. Compared to control mice, MRL/lpr mice showed higher plasma levels of anti-dsDNA antibodies, which are mainly involved in SLE pathogenesis. 2ccPA treatment decreased these levels in the MRL/lpr mice. These results suggest that 2ccPA treatment suppresses behavioral abnormalities by promoting a microglial phenotypic switch from M1 to M2 in MRL/lpr mice.

Emergence of dynamic contractile patterns in slime mold confined in a ring geometry

Coordination of cytoplasmic flows on large scales in space and time are at the root of many cellular processes, including growth, migration or division. These flows are driven by organized contractions of the actomyosin cortex. In order to elucidate the basic mechanisms at work in the self-organization of contractile activity, we investigate the dynamic patterns of cortex contraction in true slime mold Physarum polycephalum confined in ring-shaped chambers of controlled geometrical dimensions. We make an exhaustive inventory of the different stable contractile patterns in the absence of migration and growth. We show that the primary frequency of the oscillations is independent of the ring perimeter, while the wavelength scales linearly with it. We discuss the consistence of these results with the existing models, shedding light on the possible feedback mechanisms leading to coordinated contractile activity.

Stepwise slime mould growth as a template for urban design

The true slime mould, Physarum polycephalum, develops as a vascular network of protoplasm, connecting node-like sources of food in an effort to solve multi-objective transport problems. The organism first establishes a dense and continuous mesh, reinforcing optimal pathways over time through constructive feedbacks of protoplasmic streaming. Resolved vascular morphologies are the result of an evolutionarily-refined mechanism of computation, which can serve as a versatile biological model for network design at the urban scale. Existing digital Physarum models typically use positive reinforcement mechanisms to capture meshing and refinement behaviours simultaneously. While these automations generate accurate descriptions of sensory and constructive feedback, they limit stepwise design control, reducing flexibility and applicability. A model that decouples the two “phases” of Physarum behaviour would enable multistage control over network growth. Here we introduce such a system, first by producing a site-responsive mesh from a population of nutrient-attracted agents, and then by independently calculating from it a flexible, proximity-defined shortest-walk to produce a final network. We develop and map networks within existing urban environments that perform similarly to those biologically grown, establishing a versatile tool for bio-inspired urban network design.

A New Myxomycetes record (Myxogastria) from Turkey: Didymium listeri Massee

Myxomycetes called Plasmodial slime moulds, or true slime molds are eukaryotic microorganisms. They live in a variety of ecosystems. Genus Didymium Schrad. (family Didymiaceae) is a myxomycete taxon containing calcareous peridia (order Physarida) and non-calcareous capillitium. Didymium listeri Massee were recorded in this study for the first time from Turkey. D. listeri sporocarp was found in the laboratory by moist chamber culture. In addition, the description, distribution, photograph and identification key of the taxon were presented.

Tyrophagus putrescentiae (Sarcoptiformes: Acaridae) in the in vitro cultures of slime molds (Mycetozoa): accident, contamination, or interaction?

Tyrophagus putrescentiae (Schrank), commonly known as the cereal mite, cheese mite, or ham mite, is a cosmopolitan species reported from various environments in the wild, including soil, plant material and vertebrate nests. It has also been recognized as a common pest of food storages, mycological collections as well as plant and invertebrate laboratory cultures. Laboratory observations indicate that T. putrescentiae feeds on a large range of dermatophytes, yeasts and molds. We have observed the interspecific relation between this mite and several species of true slime molds (Mycetozoa) under laboratory conditions, which confirms the very broad spectrum of feeding habits of T. putrescentiae. Mycetozoans were grown in semi-sterile in vitro cultures and fed with oat flour or oat flakes. Tyrophagus putrescentiae displayed affinity to all macroscopically identifiable stages of the life cycle of Fuligo septica (L.) F.H. Wigg, Physarum polycephalum Schwein and the Didymium sp. complex [Didymium iridis (Ditmar) Fr., Didymium nigripes (Link) Fr. and Didymium bahiense Gottsb.]: live, decaying or dead plasmodia, sporangia, aethalia, spores and sclerotia. The relation carrying symptoms of various types of interspecific interaction, is hypothesized to form an evolutionarily young phenomenon, which not only identifies a new aspect of mycetozoal biology, but also presents the cereal mite as a species of high adaptive potential.

A Node Selecting Approach for Traffic Network Based on Artificial Slime Mold

The node selecting problem of traffic network is a significant issue and is difficult to be solved. In this paper, an artificial slime mold method is proposed to help us solve the problem. First, the chief components of an artificial slime mold are introduced to simulate the foraging behavior of a true slime mold, including external food sources, plasmodium, myxamoeba, nucleus, and nutrients. Then the learning mechanism of nutrient concentration for the artificial slime mold is illustrated, though there is no brain or neuron in its body. After that, the node selecting approach is described according to the propagation capabilities of nodes. Second, the algorithm flow is designed to show how to solve this kind of complex selecting problem. The algorithm flow to select important traffic nodes by artificial slime mold is composed of 4 main steps, including initialization, food searching, feeding, and selecting for output. Third, a comprehensive example is designed and derived from references to certificate that the proposed artificial slime mold can help us select important traffic nodes by their generated traffic topologies. The contributions of this paper are important both for traffic node selecting and artificial learning mechanism in theoretical and practical aspects.

Symmetry breaking transition towards directional locomotion in Physarum microplasmodia

True slime mold Physarum polycephalum has been widely used as a model organism to study flow-driven amoeboid locomotion as well as the dynamics of its complex mechanochemical self-oscillations. The aim of this work is to quantify the mechanical aspects of symmetry breaking and its transition into directional flow-driven amoeboid locomotion in small (<m) fragments of Physarum polycephalum. To this end, we combined measurements of traction stresses, fragment morphology, and ectoplasmic microrheology with experimental manipulations of cell–substrate adhesion, cortical strength, and microplasmodium size. These measurements show that initiation of locomotion is accompanied by the symmetry breaking of traction stresses and the polarization of ectoplasmic mechanical properties, with the rear part of the microplasmodium becoming significantly stiffer after the onset of locomotion. Our experimental data suggest that the initiation of locomotion in Physarum could be analogous to an interfacial instability process and that microplasmodial size is a critical parameter governing the instability. Specifically, our results indicate that the instability driving the onset of locomotion is strengthened by substrate adhesiveness and weakened by cortical stiffness. Furthermore, the Fourier spectral analysis of morphology revealed lobe number n = 2 as the consistent dominant mode number across various experimental manipulations, suggesting that the instability mechanism driving the onset of Physarum locomotion is robust with respect to changes in environmental conditions and microplasmodial properties.

Adaptive Load Balancing Ad Hoc Routing Scheme Inspired by True Slime Mold

Engineering neo-biomimetics, i.e. imitation models based on body structures and behavior of living organisms, relied upon to solve complex problems, have been studied in various fields. In distributed networks, such as ad-hoc networks and wireless sensor networks, the behavior of a variety of true slime molds which are capable of constructing multipath flow networks based on the amount of body, has been studied. Ad hoc networks only consist of mobile terminals (nodes) that can relay packets along an established route. However, link relations and the available bandwidth of the nodes change dynamically due to the mobility of nodes. In addition, the speed of communication between nodes also varies due to node positions and their communication-related quality. Thus, practical use of ad-hoc networks still remains an issue, because it is difficult to establish stable routes under such environments. This study aims to propose an adaptive load balancing routing technique that adaptively diversifies the transmission paths based on the available bandwidth, residual battery life, and the data transmission volume, by applying a mathematical model of slime mold routing, known as the physarum solver. We confirm the effectiveness of its adaptive behavior in dynamic environments using computer simulations.

Lessons from a virtual slime: marginal mechanisms, minimal cognition and radical enactivism

Radical enactivism (REC) and similar embodied and enactive approaches to the mind deny that cognition is fundamentally representational, skull-bound and mechanistic in its organisation. In this article, I argue that modellers may still adopt a mechanistic strategy to produce explanations that are compatible with REC. This argument is scaffolded by a multi-agent model of the true slime mould Physarum polycephalum.

Quantitative comparison of plasmodial migration and oscillatory properties across different slime molds

The clade of Myxogastria, commonly described as true or plasmodial slime molds, contains more than 1000 species. During their life cycle many of these slime molds develop extended networks of connected veins, known as unicellular (phanero)plasmodia. Among those, Physarum polycephalum gathered by far the most attention of biologists and physicists. Via oscillating cytoplasmic streams nutrients as well as signaling factors spread through the adaptive plasmodial network. These properties have rendered it not only a model organism for acellular slime molds, but also a model to investigate network dynamics, biological fluid-dynamics and food foraging behavior. Here, we studied parameters of plasmodial growth and network development, including chemotactic responses, in three slime mold species: Physarum polycephalum, Badhamia utricularis, and Fuligo septica. We discovered significant variations in chemotaxis, velocity, and oscillatory behavior of plasmodia among and within these species. Interestingly the patterns of the variations also reflect phylogenetic relationships of the species. In contrast to a common notion, phaneroplasmodia of slime molds develop diverse and specifically organized networks by triggers yet to be explored. This work lays the ground for studying more of these organisms to understand basic features of planar network organization and their variations, which evolved as successful solutions of nature.

Spatial mapping reveals multi-step pattern of wound healing in Physarum polycephalum

Wounding is a severe impairment of function, especially for an exposed organism like the network-forming true slime mould Physarum polycephalum. The tubular network making up the organism’s body plan is entirely interconnected and shares a common cytoplasm. Oscillatory contractions of the enclosing tube walls drive the shuttle streaming of the cytoplasm. Cytoplasmic flows underlie the reorganization of the network for example by movement toward attractive stimuli or away from repellants. Here, we follow the reorganization of P. polycephalum networks after severe wounding. Spatial mapping of the contraction changes in response to wounding reveal a multi-step pattern. Phases of increased activity alternate with cessation of contractions and stalling of flows, giving rise to coordinated transport and growth at the severing site. Overall, severing surprisingly acts like an attractive stimulus enabling healing of severed tubes. The reproducible cessation of contractions arising during this wound-healing response may open up new venues to investigate the biochemical wiring underlying P. polycephalum’s complex behaviours.

Analysis of peristaltic waves and their role in migrating Physarum plasmodia

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.

Response to various periods of mechanical stimuli in Physarum plasmodium

Response to mechanical stimuli is a fundamental and critical ability for living cells to survive in hazardous conditions or to form adaptive and functional structures against force(s) from the environment. Although this ability has been extensively studied by molecular biology strategies, it is also important to investigate the ability from the viewpoint of biological rhythm phenomena so as to reveal the mechanisms that underlie these phenomena. Here, we use the plasmodium of the true slime mold Physarum polycephalum as the experimental system for investigating this ability. The plasmodium was repetitively stretched for various periods during which its locomotion speed was observed. Since the plasmodium has inherent oscillation cycles of protoplasmic streaming and thickness variation, how the plasmodium responds to various periods of external stretching stimuli can shed light on the other biological rhythm phenomena. The experimental results show that the plasmodium exhibits response to periodic mechanical stimulation and changes its locomotion speed depending on the period of the stretching stimuli.

Self-organized mechano-chemical dynamics in amoeboid locomotion of Physarum fragments

The aim of this work is to quantify the spatio-temporal dynamics of flow-driven amoeboid locomotion in small (∼100 μm) fragments of the true slime mold Physarum polycephalum. In this model organism, cellular contraction drives intracellular flows, and these flows transport the chemical signals that regulate contraction in the first place. As a consequence of these non-linear interactions, a diversity of migratory behaviors can be observed in migrating Physarum fragments. To study these dynamics, we measure the spatio-temporal distributions of the velocities of the endoplasm and ectoplasm of each migrating fragment, the traction stresses it generates on the substratum, and the concentration of free intracellular calcium. Using these unprecedented experimental data, we classify migrating Physarum fragments according to their dynamics, finding that they often exhibit spontaneously coordinated waves of flow, contractility and chemical signaling. We show that Physarum fragments exhibiting symmetric spatio-temporal patterns of endoplasmic flow migrate significantly slower than fragments with asymmetric patterns. In addition, our joint measurements of ectoplasm velocity and traction stress at the substratum suggest that forward motion of the ectoplasm is enabled by a succession of stick-slip transitions, which we conjecture are also organized in the form of waves. Combining our experiments with a simplified convection-diffusion model, we show that the convective transport of calcium ions may be key for establishing and maintaining the spatio-temporal patterns of calcium concentration that regulate the generation of contractile forces.

Structural machines and slime mould computation

A Physarum machine is a programmable amorphous biological computer experimentally implemented in the vegetative state of true slime mould Physarum polycephalum. It comprises an amorphous yellowish mass with networks of protoplasmic veins, programmed by spatial configurations of attracting and repelling gradients. The goal of this paper to advance formalism of Physarum machines providing theoretical tools for exploration of possibilities of these machines and extension of their applications. To achieve this goal, we introduce structural machines and study their properties.

The role of noise in self-organized decision making by the true slime mold Physarum polycephalum.

Self-organized mechanisms are frequently encountered in nature and known to achieve flexible, adaptive control and decision-making. Noise plays a crucial role in such systems: It can enable a self-organized system to reliably adapt to short-term changes in the environment while maintaining a generally stable behavior. This is fundamental in biological systems because they must strike a delicate balance between stable and flexible behavior. In the present paper we analyse the role of noise in the decision-making of the true slime mold Physarum polycephalum, an important model species for the investigation of computational abilities in simple organisms. We propose a simple biological experiment to investigate the reaction of P. polycephalum to time-variant risk factors and present a stochastic extension of an established mathematical model for P. polycephalum to analyze this experiment. It predicts that—due to the mechanism of stochastic resonance—noise can enable P. polycephalum to correctly assess time-variant risk factors, while the corresponding noise-free system fails to do so. Beyond the study of P. polycephalum we demonstrate that the influence of noise on self-organized decision-making is not tied to a specific organism. Rather it is a general property of the underlying process dynamics, which appears to be universal across a wide range of systems. Our study thus provides further evidence that stochastic resonance is a fundamental component of the decision-making in self-organized macroscopic and microscopic groups and organisms.