Mechanosensation Mediates Long-Range Spatial Decision-Making in an Aneural Organism.

The unicellular protist Physarum polycephalum is an important emerging model for understanding how aneural organisms process information toward adaptive behavior. Here, it is revealed that Physarum can use mechanosensation to reliably make decisions about distant objects in its environment, preferentially growing in the direction of heavier, substrate-deforming, but chemically inert masses. This long-range sensing is abolished by gentle rhythmic mechanical disruption, changing substrate stiffness, or the addition of an inhibitor of mechanosensitive transient receptor potential channels. Additionally, it is demonstrated that Physarum does not respond to the absolute magnitude of strain. Computational modeling reveales that Physarum may perform this calculation by sensing the fraction of its perimeter that is distorted above a threshold substrate strain-a fundamentally novel method of mechanosensation. Using its body as both a distributed sensor array and computational substrate, this aneural organism leverages its unique morphology to make long-range decisions. Together, these data identify a surprising behavioral preference relying on biomechanical features and quantitatively characterize how the Physarum exploits physics to adaptively regulate its growth and shape.

Uni-cellular integration of complex spatial information in slime moulds and ciliates.

Single-celled organisms show a fascinating faculty for integrating spatial information and adapting their behaviour accordingly. As such they are of potential interest for elucidating fundamental mechanisms of developmental biology. In this mini-review we highlight current research on two organisms, the true slime mould Physarum polycephalum and the ciliates Paramecium and Tetrahymena. For each of these, we present a case study how applying physical principles to explain behaviour can lead to the understanding of general principles possibly relevant to developmental biology.

Exploiting spatial heterogeneity and response characterization in non-uniform architected materials inspired by slime mould growth.

Inspired by shape-shifting features of slime mould growth, we implement a computational algorithm to study the nutrient-induced pattern formation and transition of slime mould. We then translate the learned principles into the design and characterization of cellular materials, with particular focus on the issue of spatial heterogeneity due to the nature of the non-uniform, asymmetric pattern. Guided by clustering analysis, compression tests on 3D-printed samples, and numerical simulations by finite element models, we were able to categorize patterns with certain geometric features (such as layout and symmetry) and found similar mechanical response features, indicating high tailorability of non-uniform architected materials. This study paves the road for the advanced computer-aided design of architected materials and its potential in the development of innovative engineering mechanical devices and structural systems.

Effects of medium composition on the growth and lipid production of microplasmodia of Physarum polycephalum.

Physarum polycephalum is a plasmodial slime mold. One of the trophic stages in the life cycle of this organism is a plasmodium. In submerged culture, plasmodia are fragmented into microplasmodia. The latter both lack cell walls and are capable of rapid growth. There has been limited information on the effects of medium composition on the growth and lipid accumulation of microplasmodia. In this study, optimization of medium components by response surface methodology showed that tryptone and yeast extract concentrations had the most significant effects on lipid and biomass production; significant synergistic interactions between glucose and tryptone concentration on these responses were also recorded. The optimal medium was composed of 20 g/L of glucose, 6.59 g/L of tryptone, and 3.0 g/L of yeast extract. This medium yielded 13.86 g/L of dry biomass and 1.97 g/L of lipids. These amounts are threefold higher than those of the American Type Culture Collection (ATCC) medium. In addition, biomass and lipid production reached maximal values between only 4 and 5 days. Fatty acid compositions analysis by gas chromatography-mass spectrometer (GC-MS) revealed that P. polycephalum lipids consisted mainly of oleic acid (40.5%), linoleic acid (10%), and octadecynoic (15.8%). This is the first report on the fatty acid composition of P. polycephalum microplasmodia. These results suggest that the biomass of microplasmodia could be used as a source of material for direct conversion into biodiesel because of the absence of cell walls or it could also be used as a supplemental source of beneficial fatty acids for humans, albeit with some further evaluation needed.

Symmetry breaking and inter-clonal behavioural variability in a slime mould.

Cells are dynamic systems capable of switching from isotropic growth to polarized growth even in the absence of any pre-existing external asymmetry. Here, we study this process of symmetry breaking in the acellular slime mould Physarum polycephalum. In these experiments, slime moulds could grow on two identical opposed sources of calcium. We highlighted a positive correlation between growth dynamic, level of symmetry breaking and calcium concentration. We identified three populations of slime moulds within our clonal lineage with similar symmetry breaking behaviours but different motility characteristics. These behavioural differences between slime moulds emerged in the absence of any environmental differences. Such behavioural plasticity could generate cellular diversity, which can be critical for survival.

Transcriptome reprogramming during developmental switching in Physarum polycephalum involves extensive remodeling of intracellular signaling networks.

Activation of a phytochrome photoreceptor triggers a program of Physarum polycephalum plasmodial cell differentiation through which a mitotic multinucleate protoplasmic mass synchronously develops into haploid spores formed by meiosis and rearrangement of cellular components. We have performed a transcriptome-wide RNAseq study of cellular reprogramming and developmental switching. RNAseq analysis revealed extensive remodeling of intracellular signaling and regulation in switching the expression of sets of genes encoding transcription factors, kinases, phosphatases, signal transduction proteins, RNA-binding proteins, ubiquitin ligases, regulators of the mitotic and meiotic cell cycle etc. in conjunction with the regulation of genes encoding metabolic enzymes and cytoskeletal proteins. About 15% of the differentially expressed genes shared similarity with members of the evolutionary conserved set of core developmental genes of social amoebae. Differential expression of genes encoding regulators that act at the transcriptional, translational, and post-translational level indicates the establishment of a new state of cellular function and reveals evolutionary deeply conserved molecular changes involved in cellular reprogramming and differentiation in a prototypical eukaryote.

A biologically inspired immunization strategy for network epidemiology.

Well-known immunization strategies, based on degree centrality, betweenness centrality, or closeness centrality, either neglect the structural significance of a node or require global information about the network. We propose a biologically inspired immunization strategy that circumvents both of these problems by considering the number of links of a focal node and the way the neighbors are connected among themselves. The strategy thus measures the dependence of the neighbors on the focal node, identifying the ability of this node to spread the disease. Nodes with the highest ability in the network are the first to be immunized. To test the performance of our method, we conduct numerical simulations on several computer-generated and empirical networks, using the susceptible-infected-recovered (SIR) model. The results show that the proposed strategy largely outperforms the existing well-known strategies.

On chirality of slime mould.

Left-right patterning and lateralised behaviour is an ubiquitous aspect of plants and animals. The mechanisms linking cellular chirality to the large-scale asymmetry of multicellular structures are incompletely understood, and it has been suggested that the chirality of living cells is hardwired in their cytoskeleton. We examined the question of biased asymmetry in a unique organism: the slime mould Physarum polycephalum, which is unicellular yet possesses macroscopic, complex structure and behaviour. In laboratory experiment using a T-shape, we found that Physarum turns right in more than 74% of trials. The results are in agreement with previously published studies on asymmetric movement of muscle cells, neutrophils, liver cells and growing neural filaments, and for the first time reveal the presence of consistently-biased laterality in the fungi kingdom. Exact mechanisms of the slime mould's direction preference remain unknown.

Magnetic Nanoparticles-Loaded Physarum polycephalum: Directed Growth and Particles Distribution.

Slime mold Physarum polycephalum is a single cell visible by an unaided eye. The slime mold optimizes its network of protoplasmic tubes to minimize expose to repellents and maximize expose to attractants and to make efficient transportation of nutrients. These properties of P. polycephalum, together with simplicity of its handling and culturing, make it a priceless substrate for designing novel sensing, computing and actuating architectures in living amorphous biological substrate. We demonstrate that, by loading Physarum with magnetic particles and positioning it in a magnetic field, we can, in principle, impose analog control procedures to precisely route active growing zones of slime mold and shape topology of its protoplasmic networks.

Evaluation of Physarum polycephalum plasmodial growth and lipid production using rice bran as a carbon source.

BACKGROUND: The myxomycete Physarum polycephalum appears to have remarkable potential as a lipid source for biodiesel production. The present study evaluated the use of rice bran as a carbon source and determined the medium components for optimum growth and lipid production for this organism. RESULTS: Optimization of medium components by response surface methodology showed that rice bran and yeast extract had significant influences on lipid and biomass production. The optimum medium consisted of 37.5 g/L rice bran, 0.79 g/L yeast extract and 12.5 g/L agar, and this yielded 7.5 g/L dry biomass and 0.9 g/L lipid after 5 days. The biomass and lipid production profiles revealed that these parameters increased over time and reached their maximum values (10.5 and 1.26 g/L, respectively) after 7 days. Physarum polycephalum growth decreased on the spent medium but using the latter increased total biomass and lipid concentrations to 14.3 and 1.72 g/L, respectively. CONCLUSIONS: An effective method for inoculum preparation was developed for biomass and lipid production by P. polycephalum on a low-cost medium using rice bran as the main carbon source. These results also demonstrated the feasibility of scaling up and reusing the medium for additional biomass and lipid production.

Spectral imaging method for studying Physarum polycephalum growth on polyaniline surface.

The features of spectrophotometric scanner, generally exploited in the artwork field, are here considered in a non-conventional context to characterize the networks created by Physarum polycephalum slime mold during its motion on glass substrates covered with polyaniline: a polymer that varies its color and conductive properties according to the redox state. The used technique allowed the investigation of the effects coming out from the interaction between P. polycephalum and polyaniline. Thus, the contactless method of the analysis of polyaniline conductivity state resulted from the slime mold metabolism was suggested. Indeed, it is here demonstrated that P. polycephalum can modify properties of polyaniline due to its internal activity in contact zones.

Inhibitory effects of extracellular self-DNA: a general biological process?

Self-inhibition of growth has been observed in different organisms, but an underlying common mechanism has not been proposed so far. Recently, extracellular DNA (exDNA) has been reported as species-specific growth inhibitor in plants and proposed as an explanation of negative plant-soil feedback. In this work the effect of exDNA was tested on different species to assess the occurrence of such inhibition in organisms other than plants. Bioassays were performed on six species of different taxonomic groups, including bacteria, fungi, algae, plants, protozoa and insects. Treatments consisted in the addition to the growth substrate of conspecific and heterologous DNA at different concentration levels. Results showed that treatments with conspecific DNA always produced a concentration dependent growth inhibition, which instead was not observed in the case of heterologous DNA. Reported evidence suggests the generality of the observed phenomenon which opens new perspectives in the context of self-inhibition processes. Moreover, the existence of a general species-specific biological effect of exDNA raises interesting questions on its possible involvement in self-recognition mechanisms. Further investigation at molecular level will be required to unravel the specific functioning of the observed inhibitory effects.

Kanizsa illusory contours appearing in the plasmodium pattern of Physarum polycephalum.

The plasmodium of Physarum polycephalum is often used in the implementation of non-linear computation to solve optimization problems, and this organismal feature was not used in this analysis to compute perception and/or sensation in humans. In this paper, we focused on the Kanizsa illusion, which is a well-known visual illusion resulting from the differentiation-integration of the visual field, and compared the illusion with the adaptive network in the plasmodium of P. polycephalum. We demonstrated that the network pattern mimicking the Kanizsa illusion can be produced by an asynchronous automata-fashioned model of the foraging slime mold and by the real plasmodia of P. polycephalum. Because the protoplasm of the plasmodium is transported depending on both local and global computation, it may contain differentiation-integration processes. In this sense, we can extend the idea of perception and computation.

Physarum polycephalum percolation as a paradigm for topological phase transitions in transportation networks.

We study the formation of transportation networks of the true slime mold Physarum polycephalum after fragmentation by shear. Small fragments, called microplasmodia, fuse to form macroplasmodia in a percolation transition. At this topological phase transition, one single giant component forms, connecting most of the previously isolated microplasmodia. Employing the configuration model of graph theory for small link degree, we have found analytically an exact solution for the phase transition. It is generally applicable to percolation as seen, e.g., in vascular networks.

Futile attempts to differentiate provide molecular evidence for individual differences within a population of cells during cellular reprogramming.

The heterogeneity of cell populations and the influence of stochastic noise might be important issues for the molecular analysis of cellular reprogramming at the system level. Here, we show that in Physarum polycephalum, the expression patterns of marker genes correlate with the fate decision of individual multinucleate plasmodial cells that had been exposed to a differentiation-inducing photostimulus. For several hours after stimulation, the expression kinetics of PI-3-kinase, piwi, and pumilio orthologs and other marker genes were qualitatively similar in all stimulated cells but quantitatively different in those cells that subsequently maintained their proliferative potential and failed to differentiate accordingly. The results suggest that the population of nuclei in an individual plasmodium behaves synchronously in terms of gene regulation to an extent that the plasmodium provides a source for macroscopic amounts of homogeneous single-cell material for analysing the dynamic processes of cellular reprogramming. Based on the experimental findings, we predict that circuits with switch-like behaviour that control the cell fate decision of a multinucleate plasmodium operate through continuous changes in the concentration of cellular regulators because the nuclear population suspended in a large cytoplasmic volume damps stochastic noise.

Traffic optimization in railroad networks using an algorithm mimicking an amoeba-like organism, Physarum plasmodium.

Traffic optimization of railroad networks was considered using an algorithm that was biologically inspired by an amoeba-like organism, plasmodium of the true slime mold, Physarum polycephalum. The organism developed a transportation network consisting of a tubular structure to transport protoplasm. It was reported that plasmodium can find the shortest path interconnecting multiple food sites during an adaptation process (Nakagaki et al., 2001. Biophys. Chem. 92, 47-52). By mimicking the adaptation process a path finding algorithm was developed by Tero et al. (2007). In this paper, the algorithm is newly modified for applications of traffic distribution optimization in transportation networks of infrastructure such as railroads under the constraint that the network topology is given. Application of the algorithm to a railroad in metropolitan Tokyo, Japan is demonstrated. The results are evaluated using three performance functions related to cost, traveling efficiency, and network weakness. The traffic distribution suggests that the modified Physarum algorithm balances the performances under a certain parameter range, indicating a biological process.

Rebuilding Iberian motorways with slime mould.

Plasmodium of a cellular slime mould Physarum polycephalum is a unique living substrate proved to be efficient in solving many computational problems with natural spatial parallelism. The plasmodium solves a problem represented by a configuration of source of nutrients by building an efficient foraging and intra-cellular transportation network. The transportation networks developed by the plasmodium are similar to transport networks built by social insects and simulated trails in multi-agent societies. In the paper we are attempting to answer the question "How close plasmodium of P. polycephalum approximates man-made motorway networks in Spain and Portugal, and what are the differences between existing motorway structure and plasmodium network of protoplasmic tubes?". We cut agar plates in a shape of Iberian peninsula, place oat flakes at the sites of major urban areas and analyse the foraging network developed. We compare the plasmodium network with principle motorways and also analyse man-made and plasmodium networks in a framework of planar proximity graphs.

Routing Physarum with repellents.

Plasmodium of Physarum polycephalum is a single cell with many nuclei. Plasmodium is an easy-to-experiment-with biological substrate, a multi-functional bio-material used to implement novel and future computing architectures. The plasmodium exhibits typical features of excitable chemical systems and capable for distributed sensing, parallel information processing and decentralized actuation. Plasmodium of P. polycephalum is proved to be a universal storage modification machine. Actively growing zones of the plasmodium are considered to be elementary processors of the growing computing machine, as well as messages traveling in the spatially extended non-linear medium. Controlling propagation of the messages and computing processes is a prerequisite for a successful implementation of working prototypes of plasmodium machines. In laboratory experiments and computer simulation we show that active growing zones of plasmodium can be precisely routed using repelling diffusion gradients generated by crystals of sodium chloride. We demonstrate how to achieve controllable reflection, splitting/multiplication and merging of plasmodium's active zones.

Amoeboid organism solves complex nutritional challenges.

A fundamental question in nutritional biology is how distributed systems maintain an optimal supply of multiple nutrients essential for life and reproduction. In the case of animals, the nutritional requirements of the cells within the body are coordinated by the brain in neural and chemical dialogue with sensory systems and peripheral organs. At the level of an insect society, the requirements for the entire colony are met by the foraging efforts of a minority of workers responding to cues emanating from the brood. Both examples involve components specialized to deal with nutrient supply and demand (brains and peripheral organs, foragers and brood). However, some of the most species-rich, largest, and ecologically significant heterotrophic organisms on earth, such as the vast mycelial networks of fungi, comprise distributed networks without specialized centers: How do these organisms coordinate the search for multiple nutrients? We address this question in the acellular slime mold Physarum polycephalum and show that this extraordinary organism can make complex nutritional decisions, despite lacking a coordination center and comprising only a single vast multinucleate cell. We show that a single slime mold is able to grow to contact patches of different nutrient quality in the precise proportions necessary to compose an optimal diet. That such organisms have the capacity to maintain the balance of carbon- and nitrogen-based nutrients by selective foraging has considerable implications not only for our understanding of nutrient balancing in distributed systems but for the functional ecology of soils, nutrient cycling, and carbon sequestration.