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Heterogeneity and Delayed Activation as Hallmarks of Self-Organization and Criticality in Excitable Tissue
Self-organized critical dynamics is assumed to be an attractive mode of functioning for several real-life systems and entails an emergent activity in which the extent of observables follows a power-law distribution. The hallmarks of criticality have recently been observed in a plethora of biological...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6624746/ https://www.ncbi.nlm.nih.gov/pubmed/31333504 http://dx.doi.org/10.3389/fphys.2019.00869 |
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author | Stožer, Andraž Markovič, Rene Dolenšek, Jurij Perc, Matjaž Marhl, Marko Slak Rupnik, Marjan Gosak, Marko |
author_facet | Stožer, Andraž Markovič, Rene Dolenšek, Jurij Perc, Matjaž Marhl, Marko Slak Rupnik, Marjan Gosak, Marko |
author_sort | Stožer, Andraž |
collection | PubMed |
description | Self-organized critical dynamics is assumed to be an attractive mode of functioning for several real-life systems and entails an emergent activity in which the extent of observables follows a power-law distribution. The hallmarks of criticality have recently been observed in a plethora of biological systems, including beta cell populations within pancreatic islets of Langerhans. In the present study, we systematically explored the mechanisms that drive the critical and supercritical behavior in networks of coupled beta cells under different circumstances by means of experimental and computational approaches. Experimentally, we employed high-speed functional multicellular calcium imaging of fluorescently labeled acute mouse pancreas tissue slices to record calcium signals in a large number of beta cells simultaneously, and with a high spatiotemporal resolution. Our experimental results revealed that the cellular responses to stimulation with glucose are biphasic and glucose-dependent. Under physiological as well as under supraphysiological levels of stimulation, an initial activation phase was followed by a supercritical plateau phase with a high number of global intercellular calcium waves. However, the activation phase displayed fingerprints of critical behavior under lower stimulation levels, with a progressive recruitment of cells and a power-law distribution of calcium wave sizes. On the other hand, the activation phase provoked by pathophysiologically high glucose concentrations, differed considerably and was more rapid, less continuous, and supercritical. To gain a deeper insight into the experimentally observed complex dynamical patterns, we built up a phenomenological model of coupled excitable cells and explored empirically the model’s necessities that ensured a good overlap between computational and experimental results. It turned out that such a good agreement between experimental and computational findings was attained when both heterogeneous and stimulus-dependent time lags, variability in excitability levels, as well as a heterogeneous cell-cell coupling were included into the model. Most importantly, since our phenomenological approach involved only a few parameters, it naturally lends itself not only for determining key mechanisms of self-organized criticality at the tissue level, but also points out various features for comprehensive and realistic modeling of different excitable systems in nature. |
format | Online Article Text |
id | pubmed-6624746 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-66247462019-07-22 Heterogeneity and Delayed Activation as Hallmarks of Self-Organization and Criticality in Excitable Tissue Stožer, Andraž Markovič, Rene Dolenšek, Jurij Perc, Matjaž Marhl, Marko Slak Rupnik, Marjan Gosak, Marko Front Physiol Physiology Self-organized critical dynamics is assumed to be an attractive mode of functioning for several real-life systems and entails an emergent activity in which the extent of observables follows a power-law distribution. The hallmarks of criticality have recently been observed in a plethora of biological systems, including beta cell populations within pancreatic islets of Langerhans. In the present study, we systematically explored the mechanisms that drive the critical and supercritical behavior in networks of coupled beta cells under different circumstances by means of experimental and computational approaches. Experimentally, we employed high-speed functional multicellular calcium imaging of fluorescently labeled acute mouse pancreas tissue slices to record calcium signals in a large number of beta cells simultaneously, and with a high spatiotemporal resolution. Our experimental results revealed that the cellular responses to stimulation with glucose are biphasic and glucose-dependent. Under physiological as well as under supraphysiological levels of stimulation, an initial activation phase was followed by a supercritical plateau phase with a high number of global intercellular calcium waves. However, the activation phase displayed fingerprints of critical behavior under lower stimulation levels, with a progressive recruitment of cells and a power-law distribution of calcium wave sizes. On the other hand, the activation phase provoked by pathophysiologically high glucose concentrations, differed considerably and was more rapid, less continuous, and supercritical. To gain a deeper insight into the experimentally observed complex dynamical patterns, we built up a phenomenological model of coupled excitable cells and explored empirically the model’s necessities that ensured a good overlap between computational and experimental results. It turned out that such a good agreement between experimental and computational findings was attained when both heterogeneous and stimulus-dependent time lags, variability in excitability levels, as well as a heterogeneous cell-cell coupling were included into the model. Most importantly, since our phenomenological approach involved only a few parameters, it naturally lends itself not only for determining key mechanisms of self-organized criticality at the tissue level, but also points out various features for comprehensive and realistic modeling of different excitable systems in nature. Frontiers Media S.A. 2019-07-05 /pmc/articles/PMC6624746/ /pubmed/31333504 http://dx.doi.org/10.3389/fphys.2019.00869 Text en Copyright © 2019 Stožer, Markovič, Dolenšek, Perc, Marhl, Slak Rupnik and Gosak. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Physiology Stožer, Andraž Markovič, Rene Dolenšek, Jurij Perc, Matjaž Marhl, Marko Slak Rupnik, Marjan Gosak, Marko Heterogeneity and Delayed Activation as Hallmarks of Self-Organization and Criticality in Excitable Tissue |
title | Heterogeneity and Delayed Activation as Hallmarks of Self-Organization and Criticality in Excitable Tissue |
title_full | Heterogeneity and Delayed Activation as Hallmarks of Self-Organization and Criticality in Excitable Tissue |
title_fullStr | Heterogeneity and Delayed Activation as Hallmarks of Self-Organization and Criticality in Excitable Tissue |
title_full_unstemmed | Heterogeneity and Delayed Activation as Hallmarks of Self-Organization and Criticality in Excitable Tissue |
title_short | Heterogeneity and Delayed Activation as Hallmarks of Self-Organization and Criticality in Excitable Tissue |
title_sort | heterogeneity and delayed activation as hallmarks of self-organization and criticality in excitable tissue |
topic | Physiology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6624746/ https://www.ncbi.nlm.nih.gov/pubmed/31333504 http://dx.doi.org/10.3389/fphys.2019.00869 |
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