Cell-Cell Contact Preserves Cell Viability via Plakoglobin

Control over cell viability is a fundamental property underlying numerous physiological processes. Cell spreading on a substrate was previously demonstrated to be a major factor in determining the viability of individual cells. In multicellular organisms, cell-cell contact is likely to play a significant role in regulating cell vitality, but its function is easily masked by cell-substrate interactions, thus remains incompletely characterized. In this study, we show that suspended immortalized human keratinocyte sheets with persisting intercellular contacts exhibited significant contraction, junctional actin localization, and reinforcement of cell-cell adhesion strength. Further, cells within these sheets remain viable, in contrast to trypsinized cells suspended without either cell-cell or cell-substrate contact, which underwent apoptosis at high rates. Suppression of plakoglobin weakened cell-cell adhesion in cell sheets and suppressed apoptosis in suspended, trypsinized cells. These results demonstrate that cell-cell contact may be a fundamental control mechanism governing cell viability and that the junctional protein plakoglobin is a key regulator of this process. Given the near-ubiquity of plakoglobin in multicellular organisms, these findings could have significant implications for understanding cell adhesion, modeling disease progression, developing therapeutics and improving the viability of tissue engineering protocols

Dorsal and ventral stimuli in sandwich-like microenvironments. Effect on cell differentiation

While most of the in vivo extracellular matrices are 3D, most of the in vitro cultures are 2D--where only ventral adhesion is permitted--thus modifying cell behavior as a way to self-adaptation to this unnatural environment. We hypothesize that the excitation of dorsal receptors in cells already attached on a 2D surface (sandwich culture) could cover the gap between 2D and 3D cell-material interactions and result in a more physiological cell behavior. In this study we investigate the role of dorsal stimulation on myoblast differentiation within different poly(L-lactic acid) (PLLA) sandwich-like microenvironments, including plain material and aligned fibers. Enhanced cell differentiation levels were found for cells cultured with dorsal fibronectin-coated films. Seeking to understand the underlying mechanisms, experiments were carried out with (i) different types of dorsal stimuli (FN, albumin, FN after blocking the RGD integrin-binding site and activating dorsal cell integrin receptors), (ii) in the presence of an inhibitor of cell contractility, and (iii) increasing the frequency of culture medium changes to assess the effect of paracrine factors. Furthermore, FAK and integrin expressions, determined by Western blotting, revealed differences between cell sandwiches and 2D controls. Results show a stimuli-dependent response to dorsal excitation, proving that integrin outside-in signaling is involved in the enhanced cell differentiation. Due to their easiness and versatility, these sandwich-like systems are excellent candidates to get deeper insights into the study of 3D cell behavior and to direct cell fate within multilayer constructs.Contract grant sponsor: ERC - 306990Ballester Beltrán, J.; Lebourg, MM.; Salmerón Sánchez, M. (2013). Dorsal and ventral stimuli in sandwich-like microenvironments. Effect on cell differentiation. Biotechnology and Bioengineering. 11:3048-3058. https://doi.org/10.1002/bit.24972S3048305811Bajaj, P., Reddy, B., Millet, L., Wei, C., Zorlutuna, P., Bao, G., & Bashir, R. (2011). Patterning the differentiation of C2C12 skeletal myoblasts. Integrative Biology, 3(9), 897. doi:10.1039/c1ib00058fBallester-Beltrán, J., Cantini, M., Lebourg, M., Rico, P., Moratal, D., García, A. J., & Salmerón-Sánchez, M. (2011). Effect of topological cues on material-driven fibronectin fibrillogenesis and cell differentiation. Journal of Materials Science: Materials in Medicine, 23(1), 195-204. doi:10.1007/s10856-011-4532-zBallester-Beltrán, J., Lebourg, M., Rico, P., & Salmerón-Sánchez, M. (2012). Dorsal and Ventral Stimuli in Cell–Material Interactions: Effect on Cell Morphology. Biointerphases, 7(1), 39. doi:10.1007/s13758-012-0039-5Belkin, A. M., Zhidkova, N. I., Balzac, F., Altruda, F., Tomatis, D., Maier, A., … Burridge, K. (1996). Beta 1D integrin displaces the beta 1A isoform in striated muscles: localization at junctional structures and signaling potential in nonmuscle cells. The Journal of Cell Biology, 132(1), 211-226. doi:10.1083/jcb.132.1.211Bennett, A. M. (1997). Regulation of Distinct Stages of Skeletal Muscle Differentiation by Mitogen-Activated Protein Kinases. Science, 278(5341), 1288-1291. doi:10.1126/science.278.5341.1288Boonen, K. J. M., Langelaan, M. L. P., Polak, R. B., van der Schaft, D. W. J., Baaijens, F. P. T., & Post, M. J. (2010). Effects of a combined mechanical stimulation protocol: Value for skeletal muscle tissue engineering. Journal of Biomechanics, 43(8), 1514-1521. doi:10.1016/j.jbiomech.2010.01.039Chan, X. C. Y., McDermott, J. C., & Siu, K. W. M. (2007). Identification of Secreted Proteins during Skeletal Muscle Development. Journal of Proteome Research, 6(2), 698-710. doi:10.1021/pr060448kCharest, J. L., García, A. J., & King, W. P. (2007). Myoblast alignment and differentiation on cell culture substrates with microscale topography and model chemistries. Biomaterials, 28(13), 2202-2210. doi:10.1016/j.biomaterials.2007.01.020Chatzizacharias, N. A., Kouraklis, G. P., & Theocharis, S. E. (2008). Disruption of FAK signaling: A side mechanism in cytotoxicity. Toxicology, 245(1-2), 1-10. doi:10.1016/j.tox.2007.12.003Chen, S.-E., Jin, B., & Li, Y.-P. (2007). TNF-α regulates myogenesis and muscle regeneration by activating p38 MAPK. American Journal of Physiology-Cell Physiology, 292(5), C1660-C1671. doi:10.1152/ajpcell.00486.2006Clegg, C. H., Linkhart, T. A., Olwin, B. B., & Hauschka, S. D. (1987). Growth factor control of skeletal muscle differentiation: commitment to terminal differentiation occurs in G1 phase and is repressed by fibroblast growth factor. The Journal of Cell Biology, 105(2), 949-956. doi:10.1083/jcb.105.2.949Clemente, C. F. M. Z., Corat, M. A. F., Saad, S. T. O., & Franchini, K. G. (2005). Differentiation of C2C12 myoblasts is critically regulated by FAK signaling. American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, 289(3), R862-R870. doi:10.1152/ajpregu.00348.2004Cukierman, E. (2001). Taking Cell-Matrix Adhesions to the Third Dimension. Science, 294(5547), 1708-1712. doi:10.1126/science.1064829Cukierman, E., Pankov, R., & Yamada, K. M. (2002). Cell interactions with three-dimensional matrices. Current Opinion in Cell Biology, 14(5), 633-640. doi:10.1016/s0955-0674(02)00364-2Haba, G. D. L., Cooper, G. W., & Elting, V. (1966). HORMONAL REQUIREMENTS FOR MYOGENESIS OF STRIATED MUSCLE IN VITRO: INSULIN AND SOMATOTROPIN. Proceedings of the National Academy of Sciences, 56(6), 1719-1723. doi:10.1073/pnas.56.6.1719Di Carlo, A., De Mori, R., Martelli, F., Pompilio, G., Capogrossi, M. C., & Germani, A. (2004). Hypoxia Inhibits Myogenic Differentiation through Accelerated MyoD Degradation. Journal of Biological Chemistry, 279(16), 16332-16338. doi:10.1074/jbc.m313931200Engler, A. J., Sen, S., Sweeney, H. L., & Discher, D. E. (2006). Matrix Elasticity Directs Stem Cell Lineage Specification. Cell, 126(4), 677-689. doi:10.1016/j.cell.2006.06.044Evinger-Hodges, M. J., Ewton, D. Z., Seifert, S. C., & Florini, J. R. (1982). Inhibition of myoblast differentiation in vitro by a protein isolated from liver cell medium. The Journal of Cell Biology, 93(2), 395-401. doi:10.1083/jcb.93.2.395Florini, J. R., & Magri, K. A. (1989). Effects of growth factors on myogenic differentiation. American Journal of Physiology-Cell Physiology, 256(4), C701-C711. doi:10.1152/ajpcell.1989.256.4.c701Florini, J. R., Ewton, D. Z., & Magri, K. A. (1991). Hormones, Growth Factors, and Myogenic Differentiation. Annual Review of Physiology, 53(1), 201-216. doi:10.1146/annurev.ph.53.030191.001221Garcı́a, A. J., Vega, M. D., & Boettiger, D. (1999). Modulation of Cell Proliferation and Differentiation through Substrate-dependent Changes in Fibronectin Conformation. Molecular Biology of the Cell, 10(3), 785-798. doi:10.1091/mbc.10.3.785House, M., Daniel, J., Elstad, K., Socrate, S., & Kaplan, D. L. (2012). Oxygen Tension and Formation of Cervical-Like Tissue in Two-Dimensional and Three-Dimensional Culture. Tissue Engineering Part A, 18(5-6), 499-507. doi:10.1089/ten.tea.2011.0309Hutmacher, D. W. (2010). Biomaterials offer cancer research the third dimension. Nature Materials, 9(2), 90-93. doi:10.1038/nmat2619Ingber, D. E. (2003). Tensegrity I. Cell structure and hierarchical systems biology. Journal of Cell Science, 116(7), 1157-1173. doi:10.1242/jcs.00359Ishii, I. (2001). Histological and functional analysis of vascular smooth muscle cells in a novel culture system with honeycomb-like structure. Atherosclerosis, 158(2), 377-384. doi:10.1016/s0021-9150(01)00461-0Kislinger, T., Gramolini, A. O., Pan, Y., Rahman, K., MacLennan, D. H., & Emili, A. (2005). Proteome Dynamics during C2C12 Myoblast Differentiation. Molecular & Cellular Proteomics, 4(7), 887-901. doi:10.1074/mcp.m400182-mcp200LI, Y.-P., & SCHWARTZ, R. J. (2001). TNF-α regulates early differentiation of C2C12 myoblasts in an autocrine fashion. The FASEB Journal, 15(8), 1413-1415. doi:10.1096/fj.00-0632fjeLiu, H., Niu, A., Chen, S.-E., & Li, Y.-P. (2011). β3-Integrin mediates satellite cell differentiation in regenerating mouse muscle. The FASEB Journal, 25(6), 1914-1921. doi:10.1096/fj.10-170449Lutolf MP Hubbell JA 2005 47 55Mancini, A., Sirabella, D., Zhang, W., Yamazaki, H., Shirao, T., & Krauss, R. S. (2011). Regulation of myotube formation by the actin-binding factor drebrin. Skeletal Muscle, 1(1), 36. doi:10.1186/2044-5040-1-36Meighan, C. M., & Schwarzbauer, J. E. (2008). Temporal and spatial regulation of integrins during development. Current Opinion in Cell Biology, 20(5), 520-524. doi:10.1016/j.ceb.2008.05.010O'Connell B 2002 Oval Profile Plot. Research Services Branch, National Institute of Mental Health, National Institute of Neurological Disorders and Stroke. Available from http://rsbweb.nih.gov/ij/plugins/oval-profile.htmlPECKHAM, M. (2008). Engineering a multi-nucleated myotube, the role of the actin cytoskeleton. Journal of Microscopy, 231(3), 486-493. doi:10.1111/j.1365-2818.2008.02061.xQuach, N. L., & Rando, T. A. (2006). Focal adhesion kinase is essential for costamerogenesis in cultured skeletal muscle cells. Developmental Biology, 293(1), 38-52. doi:10.1016/j.ydbio.2005.12.040Rasband WS ImageJ U.S. National Institutes of Health, Bethesda, Maryland, USA http://imagej.nih.gov/ij/1997-2012Ren, K., Crouzier, T., Roy, C., & Picart, C. (2008). Polyelectrolyte Multilayer Films of Controlled Stiffness Modulate Myoblast Cell Differentiation. Advanced Functional Materials, 18(9), 1378-1389. doi:10.1002/adfm.200701297Rimann, M., & Graf-Hausner, U. (2012). Synthetic 3D multicellular systems for drug development. Current Opinion in Biotechnology, 23(5), 803-809. doi:10.1016/j.copbio.2012.01.011Salmerón-Sánchez, M., Rico, P., Moratal, D., Lee, T. T., Schwarzbauer, J. E., & García, A. J. (2011). Role of material-driven fibronectin fibrillogenesis in cell differentiation. Biomaterials, 32(8), 2099-2105. doi:10.1016/j.biomaterials.2010.11.057Sastry, S. K., Lakonishok, M., Wu, S., Truong, T. Q., Huttenlocher, A., Turner, C. E., & Horwitz, A. F. (1999). Quantitative Changes in Integrin and Focal Adhesion Signaling Regulate Myoblast Cell Cycle Withdrawal. The Journal of Cell Biology, 144(6), 1295-1309. doi:10.1083/jcb.144.6.1295Schlaepfer, D. D., Hanks, S. K., Hunter, T., & Geer, P. van der. (1994). Integrin-mediated signal transduction linked to Ras pathway by GRB2 binding to focal adhesion kinase. Nature, 372(6508), 786-791. doi:10.1038/372786a0SCHOEN, R. C., BENTLEY, K. L., & KLEBE, R. J. (1982). Monoclonal Antibody Against Human Fibronectin Which Inhibits Cell Attachment. Hybridoma, 1(2), 99-108. doi:10.1089/hyb.1.1982.1.99Selinummi, J., Seppälä, J., Yli-Harja, O., & Puhakka, J. A. (2005). Software for quantification of labeled bacteria from digital microscope images by automated image analysis. BioTechniques, 39(6), 859-863. doi:10.2144/000112018Smith, A. S. T., Passey, S., Greensmith, L., Mudera, V., & Lewis, M. P. (2012). Characterization and optimization of a simple, repeatable system for the long term in vitro culture of aligned myotubes in 3D. Journal of Cellular Biochemistry, 113(3), 1044-1053. doi:10.1002/jcb.23437Streuli, C. H. (2008). Integrins and cell-fate determination. Journal of Cell Science, 122(2), 171-177. doi:10.1242/jcs.018945Tamada, Y., & Ikada, Y. (1993). Effect of Preadsorbed Proteins on Cell Adhesion to Polymer Surfaces. Journal of Colloid and Interface Science, 155(2), 334-339. doi:10.1006/jcis.1993.1044Tanaka, K., Sato, K., Yoshida, T., Fukuda, T., Hanamura, K., Kojima, N., … Watanabe, H. (2011). Evidence for cell density affecting C2C12 myogenesis: possible regulation of myogenesis by cell-cell communication. Muscle & Nerve, 44(6), 968-977. doi:10.1002/mus.22224Tse, J. R., & Engler, A. J. (2011). Stiffness Gradients Mimicking In Vivo Tissue Variation Regulate Mesenchymal Stem Cell Fate. PLoS ONE, 6(1), e15978. doi:10.1371/journal.pone.0015978Wakelam, M. J. (1985). The fusion of myoblasts. Biochemical Journal, 228(1), 1-12. doi:10.1042/bj2280001Wei, W.-C., Lin, H.-H., Shen, M.-R., & Tang, M.-J. (2008). Mechanosensing machinery for cells under low substratum rigidity. American Journal of Physiology-Cell Physiology, 295(6), C1579-C1589. doi:10.1152/ajpcell.00223.2008WEISS, P. (1959). Cellular Dynamics. Reviews of Modern Physics, 31(1), 11-20. doi:10.1103/revmodphys.31.11Yamada, K. M., Pankov, R., & Cukierman, E. (2003). Dimensions and dynamics in integrin function. Brazilian Journal of Medical and Biological Research, 36(8), 959-966. doi:10.1590/s0100-879x2003000800001Zelzer, M., Albutt, D., Alexander, M. R., & Russell, N. A. (2011). The Role of Albumin and Fibronectin in the Adhesion of Fibroblasts to Plasma Polymer Surfaces. Plasma Processes and Polymers, 9(2), 149-156. doi:10.1002/ppap.20110005

Three-dimensional culture of human meniscal cells: Extracellular matrix and proteoglycan production

<p>Abstract</p> <p>Background</p> <p>The meniscus is a complex tissue whose cell biology has only recently begun to be explored. Published models rely upon initial culture in the presence of added growth factors. The aim of this study was to test a three-dimensional (3D) collagen sponge microenvironment (without added growth factors) for its ability to provide a microenvironment supportive for meniscal cell extracellular matrix (ECM) production, and to test the responsiveness of cells cultured in this manner to transforming growth factor-β (TGF-β).</p> <p>Methods</p> <p>Experimental studies were approved prospectively by the authors' Human Subjects Institutional Review Board. Human meniscal cells were isolated from surgical specimens, established in monolayer culture, seeded into a 3D scaffold, and cell morphology and extracellular matrix components (ECM) evaluated either under control condition or with addition of TGF-β. Outcome variables were evaluation of cultured cell morphology, quantitative measurement of total sulfated proteoglycan production, and immunohistochemical study of the ECM components chondroitin sulfate, keratan sulfate, and types I and II collagen.</p> <p>Result and Conclusion</p> <p>Meniscal cells attached well within the 3D microenvironment and expanded with culture time. The 3D microenvironment was permissive for production of chondroitin sulfate, types I and II collagen, and to a lesser degree keratan sulfate. This microenvironment was also permissive for growth factor responsiveness, as indicated by a significant increase in proteoglycan production when cells were exposed to TGF-β (2.48 μg/ml ± 1.00, mean ± S.D., vs control levels of 1.58 ± 0.79, p < 0.0001). Knowledge of how culture microenvironments influence meniscal cell ECM production is important; the collagen sponge culture methodology provides a useful in vitro tool for study of meniscal cell biology.</p

Hydrodynamic Regulation of Monocyte Inflammatory Response to an Intracellular Pathogen

Systemic bacterial infections elicit inflammatory response that promotes acute or chronic complications such as sepsis, arthritis or atherosclerosis. Of interest, cells in circulation experience hydrodynamic shear forces, which have been shown to be a potent regulator of cellular function in the vasculature and play an important role in maintaining tissue homeostasis. In this study, we have examined the effect of shear forces due to blood flow in modulating the inflammatory response of cells to infection. Using an in vitro model, we analyzed the effects of physiological levels of shear stress on the inflammatory response of monocytes infected with chlamydia, an intracellular pathogen which causes bronchitis and is implicated in the development of atherosclerosis. We found that chlamydial infection alters the morphology of monocytes and trigger the release of pro-inflammatory cytokines TNF-α, IL-8, IL-1β and IL-6. We also found that the exposure of chlamydia-infected monocytes to short durations of arterial shear stress significantly enhances the secretion of cytokines in a time-dependent manner and the expression of surface adhesion molecule ICAM-1. As a functional consequence, infection and shear stress increased monocyte adhesion to endothelial cells under flow and in the activation and aggregation of platelets. Overall, our study demonstrates that shear stress enhances the inflammatory response of monocytes to infection, suggesting that mechanical forces may contribute to disease pathophysiology. These results provide a novel perspective on our understanding of systemic infection and inflammation

Zwanzig-Mori projection operators and EEG dynamics: deriving a simple equation of motion

We present a macroscopic theory of electroencephalogram (EEG) dynamics based on the laws of motion that govern atomic and molecular motion. The theory is an application of Zwanzig-Mori projection operators. The result is a simple equation of motion that has the form of a generalized Langevin equation (GLE), which requires knowledge only of macroscopic properties. The macroscopic properties can be extracted from experimental data by one of two possible variational principles. These variational principles are our principal contribution to the formalism. Potential applications are discussed, including applications to the theory of critical phenomena in the brain, Granger causality and Kalman filters

Dynamic 3D Cell Rearrangements Guided by a Fibronectin Matrix Underlie Somitogenesis

Somites are transient segments formed in a rostro-caudal progression during vertebrate development. In chick embryos, segmentation of a new pair of somites occurs every 90 minutes and involves a mesenchyme-to-epithelium transition of cells from the presomitic mesoderm. Little is known about the cellular rearrangements involved, and, although it is known that the fibronectin extracellular matrix is required, its actual role remains elusive. Using 3D and 4D imaging of somite formation we discovered that somitogenesis consists of a complex choreography of individual cell movements. Epithelialization starts medially with the formation of a transient epithelium of cuboidal cells, followed by cell elongation and reorganization into a pseudostratified epithelium of spindle-shaped epitheloid cells. Mesenchymal cells are then recruited to this medial epithelium through accretion, a phenomenon that spreads to all sides, except the lateral side of the forming somite, which epithelializes by cell elongation and intercalation. Surprisingly, an important contribution to the somite epithelium also comes from the continuous egression of mesenchymal cells from the core into the epithelium via its apical side. Inhibition of fibronectin matrix assembly first slows down the rate, and then halts somite formation, without affecting pseudopodial activity or cell body movements. Rather, cell elongation, centripetal alignment, N-cadherin polarization and egression are impaired, showing that the fibronectin matrix plays a role in polarizing and guiding the exploratory behavior of somitic cells. To our knowledge, this is the first 4D in vivo recording of a full mesenchyme-to-epithelium transition. This approach brought new insights into this event and highlighted the importance of the extracellular matrix as a guiding cue during morphogenesis

Mechanobiological Modulation of Cytoskeleton and Calcium Influx in Osteoblastic Cells by Short-Term Focused Acoustic Radiation Force

Mechanotransduction has demonstrated potential for regulating tissue adaptation in vivo and cellular activities in vitro. It is well documented that ultrasound can produce a wide variety of biological effects in biological systems. For example, pulsed ultrasound can be used to noninvasively accelerate the rate of bone fracture healing. Although a wide range of studies has been performed, mechanism for this therapeutic effect on bone healing is currently unknown. To elucidate the mechanism of cellular response to mechanical stimuli induced by pulsed ultrasound radiation, we developed a method to apply focused acoustic radiation force (ARF) (duration, one minute) on osteoblastic MC3T3-E1 cells and observed cellular responses to ARF using a spinning disk confocal microscope. This study demonstrates that the focused ARF induced F-actin cytoskeletal rearrangement in MC3T3-E1 cells. In addition, these cells showed an increase in intracellular calcium concentration following the application of focused ARF. Furthermore, passive bending movement was noted in primary cilium that were treated with focused ARF. Cell viability was not affected. Application of pulsed ultrasound radiation generated only a minimal temperature rise of 0.1°C, and induced a streaming resulting fluid shear stress of 0.186 dyne/cm2, suggesting that hyperthermia and acoustic streaming might not be the main causes of the observed cell responses. In conclusion, these data provide more insight in the interactions between acoustic mechanical stress and osteoblastic cells. This experimental system could serve as basis for further exploration of the mechanosensing mechanism of osteoblasts triggered by ultrasound

Tikhonov adaptively regularized gamma variate fitting to assess plasma clearance of inert renal markers

The Tk-GV model fits Gamma Variates (GV) to data by Tikhonov regularization (Tk) with shrinkage constant, λ, chosen to minimize the relative error in plasma clearance, CL (ml/min). Using 169Yb-DTPA and 99mTc-DTPA (n = 46, 8–9 samples, 5–240 min) bolus-dilution curves, results were obtained for fit methods: (1) Ordinary Least Squares (OLS) one and two exponential term (E1 and E2), (2) OLS-GV and (3) Tk-GV. Four tests examined the fit results for: (1) physicality of ranges of model parameters, (2) effects on parameter values when different data subsets are fit, (3) characterization of residuals, and (4) extrapolative error and agreement with published correction factors. Test 1 showed physical Tk-GV results, where OLS-GV fits sometimes-produced nonphysical CL. Test 2 showed the Tk-GV model produced good results with 4 or more samples drawn between 10 and 240 min. Test 3 showed that E1 and E2 failed goodness-of-fit testing whereas GV fits for t > 20 min were acceptably good. Test 4 showed CLTk-GV clearance values agreed with published CL corrections with the general result that CLE1 > CLE2 > CLTk-GV and finally that CLTk-GV were considerably more robust, precise and accurate than CLE2, and should replace the use of CLE2 for these renal markers

The formation of actin waves during regeneration after axonal lesion is enhanced by BDNF

During development, axons of neurons in the mammalian central nervous system lose their ability to regenerate. To study the regeneration process, axons of mouse hippocampal neurons were partially damaged by an UVA laser dissector system. The possibility to deliver very low average power to the sample reduced the collateral thermal damage and allowed studying axonal regeneration of mouse neurons during early days in vitro. Force spectroscopy measurements were performed during and after axon ablation with a bead attached to the axonal membrane and held in an optical trap. With this approach, we quantified the adhesion of the axon to the substrate and the viscoelastic properties of the membrane during regeneration. The reorganization and regeneration of the axon was documented by long-term live imaging. Here we demonstrate that BDNF regulates neuronal adhesion and favors the formation of actin waves during regeneration after axonal lesion

Slime mould: The fundamental mechanisms of biological cognition

© 2018 Elsevier B.V. The slime mould Physarum polycephalum has been used in developing unconventional computing devices for in which the slime mould played a role of a sensing, actuating, and computing device. These devices treated the slime mould as an active living substrate, yet it is a self-consistent living creature which evolved over millions of years and occupied most parts of the world, but in any case, that living entity did not own true cognition, just automated biochemical mechanisms. To “rehabilitate” slime mould from the rank of a purely living electronics element to a “creature of thoughts” we are analyzing the cognitive potential of P. polycephalum. We base our theory of minimal cognition of the slime mould on a bottom-up approach, from the biological and biophysical nature of the slime mould and its regulatory systems using frameworks such as Lyon's biogenic cognition, Muller, di Primio-Lengelerś modifiable pathways, Bateson's “patterns that connect” framework, Maturana's autopoietic network, or proto-consciousness and Morgan's Canon