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    Integrated mechanisms of cellular behavior : cell biology and biological physics of the slime mold Physarum polycephalum
    In its natural habitat, the plasmodial slime mold Physarum polycephalum forms extensive transport networks that can reach up to square meters in surface area. Under laboratory conditions, small spherical microplasmodia can be produced, which are only several hundred micrometers in diameter. These fragments can be used to study the reorganization of the network, the morphology of which depends on environmental factors. When nutrients are scarce, P. polycephalum forms fan-shaped, polarized mesoplasmodia with an internal vein system instead of a stationary network with reticulated external tubes. Mesoplasmodia are migrating, autonomous and unconnected subunits, which represent a starvation-induced foraging strategy. This thesis demonstrates that the number of mitochondria correlates with the metabolic state of the cell: In the absence of glucose, the slime mold is forced to switch to different metabolic pathways, which occur inside the mitochondria. A catabolic cue which stimulates mitochondrial biogenesis is discussed. A detailed and quantitative ultrastructural description of the three main morphotypes, macro-, meso-, and microplasmodia, is provided in this thesis. These investigations provide the basis for physical models of the system. Furthermore, the present work discusses the unique motility mechanisms of mesoplasmodia: At the posterior end, lateral contraction waves pump endoplasm through the veins towards the extending front. The internal flow channel system forms a cascade of forks, which acts as a low-pass filter and causes the isotropic extension of the cellular front. This effect is analyzed by a lumped parameter model, based on the analogy of hydro-dynamic phenomena to electric circuits. The direction of locomotion is controlled via an asymmetry in the elasticity of the actin cortex. A softness gradient exists along the anterior-posterior axis, with the front being the most elastic. The slime mold is capable of constructing networks optimized for transport, and exhibits other sophisticated and complex behaviors such as decision-making, efficient foraging, and memory. The structure of the cell and its dynamics are strongly interconnected. Large-scale patterns and other phenomena, which can be observed on the entire network, are based on locally occurring cellular and molecular processes. The interplay of these mechanistic interactions, and especially the resulting intracellular fluid flow, is hypothesized to underlie the information processing which is the basis of complex behavior in P. polycephalum. The ultrastructure of the cell is the substrate on which cellular computing takes place. Therefore, an understanding of the unique cell biology of the slime mold is necessary to study emergent phenomena such as minimal cognition.
    doctoral thesis
      546  635
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    Item type:Publication,
    Choice of a unicellular organism: Physarum polycephalum
    Physarum polycephalum, a slime mould, is a unicellular organism with unique biological characteristics. One of its characteristics is the plasmodium, a vegetative state of P. polycephalum, which can be fragmented into microplasmodia and fuse back while maintaining its integrity as a unicellular organism. Starvation and a lack of glucose resulted in the formation of globular motile bodies that radially expanded, named 'Satellites', from microplasmodia, instead of a network. How these isolated fragments coordinate and reconstitute larger structures, and how this occurs without a centralized control were the main focus of this thesis. Two different approaches were taken to investigate satellite growth. The first approach was to construct models to describe the satellite growth pattern with physical parameters. The distance travelled by the satellites showed a saturating increase and was consistent between the satellites from the same patch. Therefore, negative chemotaxis from a signal molecule was considered as a mechanism of propagation. The model was constructed based on diffusion of a signal molecule from the patch, and the length scale of the diffusion front as a function of the patch size matched the displacement of the satellites. Using this model, the diffusion coefficient of the signal molecule was calculated, which was within the range of known biological signalling molecules. Also, a scaling relationship was derived based on the maximization principle, assuming that a starving organism would maximize the search area. This assumption is influenced by the optimal foraging theory, which predicts the foraging behaviour of organisms by assuming that the net energy intake is maximized. This scaling was refined with a fusion probability function, calculated based on diffusion and a typical distance between microplasmodia, as well as possible collisions between satellites. The refined scaling equations accurately described the observed number and the sizes of satellites. Based on these models, it is shown that a unicellular organism maximizes the search area even when they are fragmented, and uses a signal molecule to coordinate their behaviour.
    doctoral thesis
      261  186