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Page 1 of 21 AUTHOR SUBMITTED MANUSCRIPT - JPhysD-113621.R1
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7 Review Article
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10 Physarum polycephalum – a new take on a classic
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12 model system
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15 Christina Oettmeier1 , Klaudia Brix2 , and Hans-Günther
16 Döbereiner1
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Institute for Biophysics, University of Bremen, Otto-Hahn-Allee 1, 28359 Bremen,
19 Germany
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Jacobs University Bremen, Department of Life Sciences and Chemistry, Campus
21 Ring 1, 28759 Bremen, Germany
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E-mail: [email protected]
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August 12, 2017
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Abstract. Physarum polycephalum, literally the “many-headed” slime mold, is a
giant multi-nucleated but unicellular protist. Since the time of its first description, it
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29 has been the subject of a multitude of cell biological, biochemical, genetic, and lately
30 physical studies. The enormous size of the cell, the easy method of in vitro cultivation,
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the unique life cycle and its highly visible internal cytoplasmic streaming have made
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33 it invaluable for investigations on cell cycle regulation, differentiation, cytoskeleton
34 and locomotion. Research on P. polycephalum lost its prominent role when animal
35 cell culture and genetic techniques became more advanced, thereby replacing the slime
36 mold as a state-of-the-art model. However, research continued, driven by a small
37 number of groups, resulting in full sequencing of the slime mold’s genome, hence
38 reviving interest in studying molecular processes that enable the astounding features
39 of P. polycephalum. In recent years, research on P. polycephalum has again become
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40 cutting-edge. In 2000, Japanese researcher Toshiyuki Nakagaki performed a seminal

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experiment showing that the slime mold is able to find the shortest route through
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43 a maze. Ever since, smart problem-solving P. polycephalum has returned from the
44 shadows and is nowadays back to center-stage when questions regarding the origins of
45 intelligence and cognition are discussed. The basic mechanisms with which organisms
46 perceive their environment, integrate this information and make decisions based on
47 this input are investigated. The aim is to find underlying universal mechanisms of
48 decision making and awareness. If those mechanisms can be found in as primordial an
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49 organism as a slime mold, it could fundamentally change our perception of the nature
50 and evolution of cognition.
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53 Keywords: acellular slime mold, microplasmodium, slime mold historical perspective
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57 Submitted to: J. Phys. D: Appl. Phys.
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AUTHOR SUBMITTED MANUSCRIPT - JPhysD-113621.R1 Page 2 of 21
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3 Physarum polycephalum – a new take on a classic model system 4
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5 to plasmodia) [5, 6], cell cycle regulation [7–9], and DNA replication. Furthermore, its
6 macroscopic size facilitates research on the cytoskeleton and locomotion [10,11], environ-
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8 mental sensing and response (photo- and chemotaxis) [12, 13]. Comprehensive reviews
9 on the above topics were compiled by Aldrich & Daniel 1982 [14], Sauer 1982 [15] and
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10 Burland 1993 [16].
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13 The high genetic stability of the slime mold’s numerous nuclei, its synchronous mitotic
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cycle and its mechanism of DNA synthesis have inspired cancer researchers [17–19], who
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16 tested antitumor compounds on it. P. polycephalum was a very helpful model organism
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17 for research before cell culture techniques and tissue engineering advanced. It could be
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19 grown axenically in large quantities [20] of up to 100 liters, therefore providing enough
20 material for biochemical analyses. Since a macroplasmodium is a coenocyte, all nuclei
21 are clones of each other. This notion explains why molecular biologists value P. poly-
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cephalum so much, namely because it provides an extraordinary level of reproducibility.
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While research on P. polycephalum created new insight into the biology and physics
of cells, progress in mammalian and bacterial cell culture in the 1970s and 80s soon
exceeded it. For example, viruses could be replicated in infected human cells in vitro.
Therefore, vaccines could be developed in large quantities using cell culture technologies.
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Furthermore, genetic engineering (recombinant DNA technology) advanced in the 1970s.
31 For the first time, mammalian genes could be expressed in bacteria and soon after, ge-
32 netically engineered animal cells were developed to produce more complex recombinant
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34 proteins, e.g. antibodies, for therapeutic and research purposes. A spectacular innova-
35 tion was the production of recombinant human insulin, which was first marketed in the
36 United States in 1982. Regarding these developments in molecular and cell biology, it
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38 is understandable that research on P. polycephalum took a back seat for a while.
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Despite the lack of a nervous system or even neuronal network-like information pro-
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42 cessing structures, P. polycephalum can solve mazes [21], geometrical puzzles [22] and
43 features memorizing ability, both internally [23] and externally [24]. ‘External memory’,
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in this context, means the ability of the slime mold to recognize its own trail. A slime
46 trace is left behind on the substrate, and when the organism encounters this slime de-
47 posit again, it avoids these already covered areas during foraging. Furthermore, it can
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49 make ’smart’ decisions while distinguishing between different food sources [25]. When
50 it comes to foraging, P. polycephalum can perform complex risk-management tasks,
51 and considers different choices before making optimal decisions in taking the correct
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53 route [26, 27]. This hints to a rudimentary form of intelligence which is usually only
ascribed to organisms having a higher level of neurological sophistication. Recent re-
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search has also included unconventional computing for path finding [28,29] and even the
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57 control of robots by P. polycephalum [30]. A comprehensive review of the wide range of
58 sensing and computing devices implemented with P. polycephalum is given by [31].
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The first to test P. polycephalum’s maze-solving abilities was the Japanese researcher
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5 Toshiyuki Nakagaki in the early 2000s [21]. He allowed a plasmodium to cover an ex-
6 tensive labyrinth, before placing oat flakes at the entry and the exit. The slime mold
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8 quickly rearranged its veins until only the most efficient path between the two food
9 sources remained. This is an astounding feat for a brainless organism. In a subsequent
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10 experiment, Nakagaki and coworkers arranged the oat flakes into an approximation of
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12 the geography of Tokyo and its surrounding cities [32]. The plasmodium grew out from
13 its origin at the initial food source, and progressively reached out for colonizing each
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of the surrounding food sources. The spreading network of tubes connected all hubs
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16 consisting of oat flakes and finally P. polycephalum managed to form a network of veins
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17 that was shaped very similar to the existing railway system, demonstrating again its
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19 ability to create cost-efficient networks in a self-organized fashion. In terms of the slime
20 mold network, cost-efficiency means a low total length of veins with yet a short aver-
21 age minimum distance between food sources. The experiment has since been repeated,
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simulating many man-made structures, ranging from highways [33] to wireless sensor
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networks [34]. As an alternative solution to Nakagaki’s maze experiment, it has been
demonstrated that P. polycephalum can also solve a maze in one pass, i.e. without
previously exploring the whole area of a given maze [28]. The prerequisite is only that
a chemo-attractant is placed at the destination site. This flexibility in behaviour high-
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lights the slime mold’s suitability as a substrate for biological computing. Biologically
31 inspired, highly efficient algorithms can be extracted from observing the formations built
32 by the slime mold. The design of a transportation network takes into account fault tol-
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34 erance, i.e. the ability of the network to cope with disturbances and disconnections.
35 This parameter, called robustness, involves among other factors redundant connections.
36 The trade-off between robustness and cost-efficiency is a recurring problem in network
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38 design. Living creatures have optimized their transport networks (e.g. vascular systems
39 of plants and animals, foraging and migration patterns) through evolution over millions
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of years. Therefore, solutions from nature can be helpful and inspiring to human de-
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42 sign. P. polycephalum’s network can be described as the outcome of natural biological
43 computation, creating a robust and efficient transport network.
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46 3. Neither a plant, nor belonging to fungi or animals – amoebozoa are
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50 Research on P. polycephalum is as versatile as the organism itself. The fact that the
51 slime mold’s sporangia look so much like the fruiting bodies of fungi have led to their
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early inclusion into the fungal kingdom. Furthermore, P. polycephalum feeds on organic
material from e.g. decomposing plants, emulating a saprophytic lifestyle typical for
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55 fungi. However, slime molds are neither plants, nor animals or fungi, but have certain
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57 traits in common with all of these groups. By way of example, under non-favorable en-
58 vironmental conditions, P. polycephalum forms a sclerotium, an inactive dormant state
59 that can be reversed and reactivated by adding water and nutrients. Sclerotia formation
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allows P. polycephalum to survive in a dormant state for several years. The robust walls
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5 of the sclerotium contain cellulose [35], a molecular feature of plants.
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8 The pigments which give P. polycephalum its exquisite yellow color seem to be unique to
9 the organism. So far, several pigments have been identified [36–38]. Some of them serve
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10 as photoreceptors. P. polycephalum responds to UV and visible light by exerting neg-
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12 ative phototaxis and light-induced morphogenesis (sporulation of starving plasmodia).
13 Light sensing is mediated by phytochromes, and several such blue and UV light per-
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ceiving molecules feed information into signal transduction pathways, thus controlling
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16 basic cellular functions [39]. Hence, the physiology of P. polycephalum’s photo-sensing
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17 shares motifs from both plants and animals; phytochromes and blue light receptors play
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19 a role in higher plant development, whereas the light-induced sporulation pathways and
20 negative phototactic motility responses are found in animal cells as well.
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Furthermore, the numerous mitochondria, evolutionary understood as endosymbionts,
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are of the tubular type, which is typically found in fungi and other protozoa [40]. In
addition, mitochondrial fission follows a synchronized cycle [41] – like nuclear divisions.
The mitochondrial genome has been completely sequenced [42], revealing extensive RNA
editing and biparental inheritance of mitochondria, which otherwise only occurs in some
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yeasts and fungi.
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32 In the past, scientists curious to learn more about the huge and fast moving giant
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34 amoeboid organism P. polycephalum sent it to space [43], coincidentally aboard the last
35 successful mission of the space shuttle “Challenger”. A few years later, the German as-
36 tronaut Ulf Merbold performed experiments with P. polycephalum in space again [44].
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38 The goal of these experiments was to determine P. polycephalum’s ability to react to
39 gravity (graviresponse). Down on Earth, another bench-marking demonstration was
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performed in the 1990s at the University of Bonn in Germany. In honor of Karl-Ernst
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42 Wohlfarth-Bottermann, then the Director of the University’s Institute of Cytology and
43 Micromorphology, the slime mold was grown on oat flakes laid out in a W-shaped filter
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paper-covered device (see Figure 1a in [45]). It was at about this time that research
46 on P. polycephalum spread from Japan to Europe and the Americas. The W-shaped
47 specimen covered a surface area of 5.5 m2 at the end of the experiment and weighed
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49 approximately 3 kg, which earned it the title of largest single cell ever grown, worth
50 a lasting entry into the Guinness Book of Records in 1989 [46]. The 3 kg of biomass
51 were used for subsequent biochemical experiments, in support of research efforts towards
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53 understanding the molecules enabling P. polycephalum’s astonishingly fast, precise, and
decisive movement, that is, by a rhythmic shuttle streaming with a periodicity in the
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minutes-range.
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58 From an evolutionary and taxonomic perspective, slime molds still offer challenges. P.
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polycephalum is a member of the myxogastria, which are characterized by the formation
of syncytial plasmodia (i.e. plasmodia composed of a single cell). They are linked by
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5 common evolutionary ancestry to cellular slime molds, with Dictyostelium discoideum
6 being the most prominent model organism among them. Myxogastria and Dictyostelia
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8 differ in several important aspects. The vegetative state of D. discoideum is a haploid
9 solitary feeding stage. Sexual reproduction is preceded by aggregation and subsequent
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10 fusion of the cells (for reviews on D. discoideum, see [47] and [48]). In contrast, the
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12 vegetative state of P. polycephalum is a large coenocyte with diploid nuclei, which dif-
13 ferentiates into fruiting bodies producing haploid spores. The phenotypic characteristics
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of such fruiting bodies have been the main tool of classification in myxogastria. So far,
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16 agreement with evolutionary reconstruction is based upon DNA sequence data [49, 50].
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17 At the finer resolution of relatedness between species and genera, traditional systemat-
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19 ics began to falter. Molecular evidence even blurred the concept of genera by providing
20 evidence that the genus Physarum is not uniform, with Badhamia utricularis as a close
21 relative of P. polycephalum [51]. Sampling of B. utricularis globally, for subsequent
22
tests to understand geographic diversification, revealed this species as emerging from at
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found in other widespread genera as well. an
least two different “cryptic” species [52]. It is likely that such cryptic diversity will be
The ability of D. discoideum to produce viable offspring from cross breeding of different
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genotypes of established lab strains is narrow [53]. These limitations explain the compli-
31 cations occurring when strain-crossing experiments with cellular slime molds were per-
32 formed. On the other hand, hybridizing different strains is well possible among P. poly-
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34 cephalum, thereby facilitating the generation and analysis of numerous mutants [54,55].
35 Since a few years, transformation of D. discoideum with plasmid DNA is possible [56],
36 but this technique has not been realized so far for P. polycephalum. Hence, it is still
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38 not possible to use classic means of genetic modification on P. polycephalum, hindering
39 transient transfection or stable transduction experiments. There is, however, hope to
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establish state-of-the-art genome editing systems for genetic manipulation of P. poly-
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42 cephalum. Such experiments will be instructive with regard to overcoming the robustness
43 of P. polycephalum to genetic manipulation, or, in other words, in understanding its im-
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pressive genetic stability.
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47 Despite some limitations for experimental work with P. polycephalum, genome sequenc-
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49 ing has been achieved [57]. The slime mold’s genome is comprised of 188 million nu-
50 cleotides, encoding 34,000 genes, which is over 50 percent more than the human genome
51 has. The genome of P. polycephalum revealed unexpected insights into early evolu-
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53 tion of eukaryotes such as an astonishingly early emergence of tyrosine kinase-mediated
signaling [58]. This pathway, previously considered important for the developing mul-
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ticellularity in animals, has apparently been lost in the genomes of fungi and other
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57 amoebozoa such as D. discoideum [59].
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Slime molds, in particular P. polycephalum, have been grown in laboratories around
the world for many decades. The question therefore arises to what extent such strains
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5 maintained differences due to inbreeding, similar to phenomena observed in yeasts [60].
6 Adaptation was made responsible for easy cultivability of P. polycephalum amoebae
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8 on simple media [61]. However, and forward-looking, it would be interesting to find
9 out how quickly strains diverge upon continuous subculturing of plasmodia. In light
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10 of its long history as an in vitro-cultured giant amoeba featuring high genetic stability
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12 as such, P. polycephalum would be a good candidate as model organism in studies on
13 microevolution.
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16 4. Laying of the cornerstone: Locomotion – function follows structure
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18 The foundations for many more recent discoveries were established decades ago. In par-
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20 ticular, studies on the locomotion machinery and the cytoskeleton of P. polycephalum,
21 which enable its characteristic oscillations, provide an important basis for establishing
22
the acellular slime mold as a model organism.
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One of the most prominent features of P. polycephalum is its motility. Since the or-
ganism is so big, its internal movements are easily visible, even with the naked eye.
Shuttle streaming, i.e. the movement of endoplasm (fluid cytoplasm) through veins
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29 and the conversion from endo- to ectoplasm (gel-like rigid cytoplasm) in certain zones
30
31 was one of the first phenomena to be described. Shuttle streaming has been discov-
32 ered early on [62, 63]. At first, the origins of the contraction-relaxation cycles were
33
not clear. Contractile fibrils were identified [64], and soon a correlation between the
34
35 fibrillary structures and the motive force generator driving the shuttle streaming was
36 established [65–71]. It became clear soon after that the filaments consisted of F-actin
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38
and that the motor protein was myosin [72]. Once this was established, the search for an
39 underlying biochemical oscillator began which would explain the regular and rhythmic
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40 contraction-relaxation cycles of P. polycephalum’s acto-myosin system. Simultaneously,

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42 the ultrastructure was investigated further. The research efforts were focused on uncov-
43 ering the components of the cytoskeleton of P. polycephalum in order to compare the
44 rapidly emerging knowledge with data gained from other model organisms used in cell
45
46 biology. Many groups [73–78] contributed extensively to this topic during the late 1970s
47 and 1980s. The research endeavor proved right in fulfilling its promises for the future,
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as we now understand how actin and myosin interact with each other to bring about
49
50 the cytoplasmic shuttle streaming that is so unique and special for P. polycephalum [79].
51
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As a next step, the giant plasmodial network had to be miniaturized. At first, this
might seem trivial, but reproducibly creating smaller units of the phaneroplasmodia
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55 remains a difficult task. Depending on the research question at hand, either isolated
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57 endoplasmatic drops, isolated actomyosin threads or microplasmodia can be used.
58
59 Particularly for light and electron microscopic investigations and biochemical experi-
60
ments, it was necessary and useful to develop smaller models of P. polycephalum. When
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5 a vein is punctured, the endoplasm pours out due to the high intracellular pressure
6 and forms so-called protoplasmic drops [80, 81]. These can be taken off the strands
7
8 after a couple of minutes for further analysis. Characteristic for protoplasmic drops
9 is the rapid creation of new plasma membrane and the formation of invaginations and
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10 vacuoles within 10 to 15 min. If the protoplasmic drops are incubated in a caffeine-
11
12 containing medium, they will form spheres enclosed in a plasma membrane without any
13 invaginations, producing so-called caffeine droplets [82–84]. Actomyosin threads can be
14
generated by squeezing out the endoplasm into water [85]. These threads enable in
15
16 vitro studies of actin and myosin over several contraction and relaxation cycles, and
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17 were useful in analyzing molecular events in cell motility, e.g. the role of ATP [86].
18
19
20 Alternatively, P. polycephalum can be maintained in constantly agitated axenic cultures,
21 whereby shear forces create so-called microplasmodia [87,88]. This system is more repro-
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ducible than cutting off pieces from a macroplasmodium, because a macroplasmodium
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is not homogenous. There are chemical gradients, and cell organelles might not be dis-
tributed evenly. A great number of microplasmodia can be produced from one single
macroplasmodium put into a shaking liquid culture. Shear forces tear the plasmodium
apart, and after one or two days, equally sized microplasmodia appear. Their size is de-
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pendent upon the shaking speed. Microplasmodia, because they float freely in nutrient
31 medium, have an actin network different from that of macroplasmodia grown on a solid
32 substrate [78]. From the investigations of microplasmodia from shaking cultures, in-
33
34 sights into the formation of early networks could be gleaned. When microplasmodia are
35 plated upon a solid agar surface, they fuse locally and give rise to a connected network
36 via a percolation transition [89, 90]. The shape of the networks is strongly dependent
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38 on environmental parameters, e.g. softness of substrate, nutrient and repellent concen-
39 trations [91].
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42 Undisputed, the interactions between actin and myosin, specifically in the cortical cy-
43 toskeleton beneath the plasma membrane, are responsible for the relaxation-contraction
44
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cycles observed in macro- and microplasmodia of P. polycephalum (e.g. [77, 78]). How-
46 ever, the search for the biochemical or primary oscillator is still ongoing. While it is
47 highly likely that biochemical processes lie at the heart of the notional oscillator, it
48
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49 is also possible that hydrodynamic interactions alone account for the observed oscilla-
50 tions [92]. This notion is reflected by some physical models, see section 5. Genetically
51 encoded cellular rhythms are generated by complex interactions among macromolecules
52
53 like cytoskeletal proteins, ions and metabolites. Such biochemical oscillators control
every aspect of cell physiology and encompass signaling, motility and development. An
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example of an inherently oscillatory process is glycolysis. In P. polycephalum, the in-
56
57 hibition of glycolysis leads to a significant change in the oscillation period [93]. The
58 comprehensive oscillatory system of cytoskeletal elements and biochemical pathways is,
59
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however, intricate and involves many parameters (figure 3). Energy metabolism, mi-
tochondria and calcium ions are involved, as well as the contractile elements of the
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Figure 3. Proposed oscillatory network (modified after [93]).
physiological oscillator governing rhythmic contractile phenomena.
Model of the
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31
32 cytoskeleton, and their molecular regulators. It is this interplay that creates the observ-
33 able force output.
34
35
36 Involved in the interaction between actin and myosin are calcium ions, since P. poly-
37 cephalum myosin binds calcium, and becomes inhibited by high concentrations [11, 94].
38
Thus, it was postulated that the contraction mechanism is unlike that in e.g. muscle
39
cells, where calcium is strictly required for the interactions between myosin and actin
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41 molecules, but resembles that in plants (e.g. the alga Chara) and other lower eukaryotes,
42
43 where the two proteins also interact in the absence of calcium. However, this interac-
44 tion (binding and dissociation) and its inhibition might well be dependent on varying
45 concentrations of free calcium ions. It is certain, however, that calcium plays a promi-
46
47 nent role in the contraction-relaxation cycle. Evidence for a calcium binding site on
48 the light chain of myosin has been found [95]. Calcium oscillations have been described
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49 frequently in P. polycephalum (e.g. [96–98]). This underlines the importance of calcium

50
51 (as Ca2+ ) as ubiquitous second messenger with wide-ranging physiological roles. These
52 include the aforementioned muscle contraction, neuronal transmission processes, cellular
53
motility and fertilization of egg cells. It is important in cell growth and proliferation,
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55 and equally essential for the rapid oscillating motion allowing P. polycephalum to move
56 and make its decisions for survival.
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60
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5 5. Physical Models
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7 Recognizing the regularities of oscillatory phenomena in P. polycephalum and in ac-
8
9 knowledging the actomyosin system as the driving force, questions about the biochemical
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10 nature and the spatiotemporal self-organization of mechanochemical activity emerged.
11 Modeling supports assessments of the physics of self-organization, self-sustained (or
12
13 auto-) oscillations, cytoplasmic streaming, and lastly, amoeboid motility. The purpose
14 of creating models is to understand in simpler, albeit more abstract, terms how and
15
16
why cells oscillate and move about. Several models have been suggested, the earliest
being the proposal that the cell cycle of P. polycephalum is driven by a relaxation oscil-
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18 lator [99, 100].
19
20
21 Rhythmic oscillations are locally very well coordinated along the plasmodial body, so
22 that they collectively and sequentially produce a gradient of pressure. This gradient
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induces protoplasmic streaming towards the leading edge (’front’) of the plasmodium.
Interestingly, the slime mold uses peristalsis to drive internal cytoplasmic flows. Peri-
stalsis is caused by a wave of cross-sectional contractions along a tube. Neighboring
areas are more in phase than tubes that are further apart in the network, and when the
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29 wavelength of the peristaltic wave is of the order of the size of the network, regardless of
30
31
overall network size, transport is optimized [101]. It is puzzling, though, how the slime
32 mold can measure its own size and adjust the peristaltic wavelength accordingly. It is
33 suspected that signaling molecules are involved, which are triggered by a stimulus (e.g.
34
35 food). The signaling molecules then cause a feedback loop by increasing the local con-
36 traction amplitude, thereby generating enhanced cytoplasmic flow to propagate further
37 into the network, where the process is repeated [102].
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39
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40 When it comes to modelling the observed oscillation patterns, opinions diverge. Two
41
general schools of thought are pointed out, namely a biochemically centered explana-
42
43 tion, and another, based on mechanochemical oscillations. A prominent example of
44 a calcium-driven mechanism was postulated by Smith and Saldana in 1992 [103]. In
45
46
short, their model explains shuttle streaming in the veins of P. polycephalum to de-
47 pend on phosphorylation-dephosphorylation cycles on the motor protein myosin. In
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this model, relaxation and contraction cycles are believed to be mainly driven by the
49
50 exchange of calcium between the cytosol and intracellular storage compartments (like
51 the endoplasmatic reticulum and the mitochondrial matrix). Later, this model was
52 modified by taking flow and deformation into account [104]. Other models were put
53
forward early on, which focused on the chemical aspects of the oscillator. In spite of its
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55 unknown nature, coupled phase-oscillator models are mentioned consistently [105–107].
56
A reaction-diffusion-advection model was also postulated [108], which considers diffu-
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58 sion as well as advection of the endoplasm.
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Another set of models focuses on the assumption that spatial coordination can be
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4
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5 achieved by mechanical interactions between different regions (e.g. [109]). V.A. Teplov
6 developed a model according to which self-excited mechanochemical oscillations occur
7
8 when the external load exceeds a critical value [110]. The activation of mechanical
9 stress-induced membrane-bound receptor proteins (which are typically found in other
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10 cellular systems) and the subsequent activation of intracellular messengers, which then
11
12 trigger the cytoskeleton, are central to this model. The advantage of this particular
13 model in mechanistically explaining the shuttle streaming of the giant P. polycephalum
14
is given by its validity for large-sized systems. Diffusion and convection are not limiting
15
16 factors, but mechanical, i.e. hydrodynamical connections, play the dominant role. The
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17 hypothesis is that local positive feedback between deformation and contraction of the
18
19 contractile apparatus exists. Thus, hydrodynamic interaction alone, between different
20 regions of the strand via the streaming endoplasm, is capable of inducing the observed
21 characteristic contractile behavior [92]. In this latter aspect, earlier hypotheses also
22
took hydro-dynamical changes into consideration in explaining periodic contraction-
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relaxation cycles of miniature models derived from P. polycephalum [83].
However, the truth may lie between both classes of models. For example, a reaction-
diffusion based model [111] focuses on biochemical processes but takes into account
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30
hydrodynamic flow effects. Other chemo-mechanical models have also been constructed
31 [112]. The viscoelasticity and stiffness of the cytoplasm are important features that were
32 integrated into more recently proposed models [113, 114]. Based on experiments with
33
34 migrating fragments of P. polycephalum, a model has been costructed which includes
35 forces from the viscous endoplasm, a poro-elastic, contractile cytoskeleton and adhesive
36 interactions with the substrate [115]. The coordinated influences of these factors seem to
37
38 be responsible for the observed locomotion. In addition, the extensive system of plasma
39 membrane invaginations of plasmodial veins might allow for fine-tuned adjustments by
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means of localized surface extension and reduction.
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42
43 As mentioned above, P. polycephalum exhibits intelligent characteristics, e.g. during
44
45
foraging, where it is capable of solving the shortest path problem. The slime mold
46 also has some form of memory. Given the absence of a nervous system, there has been
47 considerable interdisciplinary interest in understanding the rules that govern its behav-
48
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49 ior. Memory, for example, can be modeled as a set of differential equations [116]. It
50 can, however, also be modeled as the response of a simple electronic circuit [117]. The
51 material properties of the slime mold, i.e. the elasticity of its membranes and cytoskele-
52
53 ton, and the fluid flow inside the veins, lend itself to the construction of an equivalent
electrical circuit made up of passive elements such as resistors, capacitors and induc-
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tors. Together, they form a circuit which can ’learn’ and predict subsequent signals. A
56
57 simplification, but it is an elegant one, which reduces the complexity of the biological
58 system while still being useful in examining primitive intelligence.
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60
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5 6. The arts of Physarum polycephalum
6
7 BioArt is an artistic genre that emerged in the 1980s. It exploits the relationship be-
8
9 tween science and art by, for example, using living matter as a new medium. Unforeseen
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10 forms of beauty and understanding arise from scientific progress in biology and the life
11 sciences, but also unexpected risks and ethical questions. BioArt takes up this am-
12
13 bivalence and materializes and visualizes it. The genre is varied. Historically, plants
14 and animals have appeared in numerous works of art. In a long and ongoing process,
15
16
humans have even influenced the evolution of plants and animals by selective breeding
and domestication, creating e.g. ornamental flowers and various breeds of pets, selected
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18 and appreciated for their aesthetic value [118]. Thus, the idea that organisms could be
19
20 art is not new. Today, artists also work with bacteria, fungi, slime molds, and cell lines
21 that have been genetically modified and only exist in laboratories. Such manipulations
22 require collaborations with scientists and access to laboratories. By dealing with e.g.
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biotechnology, synthetic biology, genetics and biomedicine, BioArt can also serve as a
way to communicate scientific developments to the public and to initiate ethical discus-
sions. An overview and an introduction into BioArt is given by the book ‘Signs of Life:
Bio Art and Beyond’ by Eduardo Kac [119].
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31
The beauty and fascination of P. polycephalum, this long-lived giant amoeba, has even
32 inspired a growing number of artists who include the slime mold into their works of art
33 and performances. The plasmodial network of P. polycephalum in itself is fascinating,
34
35 and many scientific experiments, e.g. the observation of foraging patterns or network
36 growth, possess a certain aesthetic quality. Therefore, it is not surprising that the slime
37 mold has been embraced by the arts (figure 4). The slime mold has become a collabora-
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39
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58 Figure 4. Left: “Bodymetries. Visitor at the installation at Prix Cube exhibition
59 (2014)” by Theresa Schubert [120]. Right: “Slime Mould Seeking Food” by Heather
60 Barnett.
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5 tor and performer in artistic endeavors. While growing inside, under and on sculptural
6 art work, P. polycephalum is being used as a living material and an inspiration alike.
7
8 Questions that interest researchers are also asked by artists, such as what can be learned
9 from a primordial organism about decentralized cooperation and the limits of conscious-
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10 ness. By using living slime molds as art material, connections can be made between the
11
12 different ways humans and non-sentient beings like the slime mold experience life. Or,
13 in simpler terms: “How does the slime mold know what it knows? How do we know
14
what we know?” [121].
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16
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17 The experiment “Being Slime Mold© ”, devised in 2013 by British artist Heather Barnett
18
19 in collaboration with the journalist Daniel Grushkin, is a participatory experiment in
20 which groups of people emulate the behavior of the slime mold by obeying simple rules.
21 The 2014 documentary titled “The Creeping Garden” by Tim Grabham and Jasper
22
Sharp shows that the growing, moving slime mold is aesthetically pleasing and very
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fascinating. German artist Theresa Schubert is also embracing the slime mold when
creating pieces of art, for example by projecting its sophisticated network of veins onto
human skin. Together with Andrew Adamatzky, they published the book “Experiencing
the Unconventional: Science in Art” [122] which aims to bring together art, digital me-
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dia projects, molecular biology and computer sciences, but also physics, chemistry, and
31 robotic science. The slime mold is a unique organism, in that it inspires and extends
32 into each and all of these areas. A fascinating workshop, Nodes & Networks [123], has
33
34 been designed by Heather Barnett around the First International Physarum Transport
35 Networks Workshop (PhysNet), held as part of BICT (9th Conference on Bio-Inspired
36 Information and Communications Technologies) from December 3 – 5 2015 at Columbia
37
38 University in New York City. An array of diverse individuals were discussing and creat-
39 ing interactions of arts and science. Amongst others, artists, physicists, a geneticist, an
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urban architect, a bee ecologist, an internet researcher, and a games designer, mingled
41
42 for three days to come up with an ad hoc project in order to interact with the interested
43 public on a Sunday. A write up of this adventure can be found in the August 2016 issue
44
45
of SciArt Magazine [124].
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47
7. Conclusion
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50 In summary, P. polycephalum is a versatile model organism that, despite decades of
51 research, still holds some challenges in store. In particular, advancements in the subject
52
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of genetics will shed light onto the complicated processes of cell cycle regulation,
metabolism and signaling pathways. The complex behavior of P. polycephalum is
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55 currently another research focus. By studying how a brainless and rather simple
56
57 organism navigates its environment and makes optimal decisions securing its survival,
58 the broader question of an underlying universal mechanism of decision-making arises.
59 The goal is not only to describe the behavioral pattern in response to environmental
60
cues, but also how this information is perceived and processed within the slime mold.
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4
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5 To answer these questions, the role of fluid flow and oscillations within the veins
6 has to be investigated in order to get a detailed picture of network dynamics and
7
8 motility. Present research on this fundamental topic is highly interdisciplinary and even
9 extends to artificial intelligence and robotics. Furthermore, membrane-bound sensors
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10 and molecular signaling pathways need to be identified in order to complete our picture
11
12 of the slime mold as a whole.
13
14
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Home Search Collections Journals About Contact us My IOPscience

Physarum polycephalum - a new take on a classic model system

Manuscript version: Accepted Manuscript

This Accepted Manuscript is: © 2017 IOP Publishing Ltd

40 cutting-edge. In 2000, Japanese researcher Toshiyuki Nakagaki performed a seminal

40 contraction-relaxation cycles of P. polycephalum’s acto-myosin system. Simultaneously,

49 frequently in P. polycephalum (e.g. [96–98]). This underlines the importance of calcium

40 calcium inhibition of the actomyosin system of a lower eukaryote, Physarum polycephalum.

with plasmid DNA. Nat. Protoc., 2(6):1317–1324, 2007.

[78] K. Brix, J. Kukulies, and W. Stockem. Studies on microplasmodia of Physarum polycephalum.

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