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Astrocytes Increase ATP Exocytosis Mediated Calcium Signaling in Response to Microgroove Structures
Following central nervous system (CNS) injury, activated astrocytes form glial scars, which inhibit axonal regeneration, leading to long-term functional deficits. Engineered nanoscale scaffolds guide cell growth and enhance regeneration within models of spinal cord injury. However, the effects of mi...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4297955/ https://www.ncbi.nlm.nih.gov/pubmed/25597401 http://dx.doi.org/10.1038/srep07847 |
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author | Singh, Ajay V. Raymond, Michael Pace, Fabiano Certo, Anthony Zuidema, Jonathan M. McKay, Christopher A. Gilbert, Ryan J. Lu, X. Lucas Wan, Leo Q. |
author_facet | Singh, Ajay V. Raymond, Michael Pace, Fabiano Certo, Anthony Zuidema, Jonathan M. McKay, Christopher A. Gilbert, Ryan J. Lu, X. Lucas Wan, Leo Q. |
author_sort | Singh, Ajay V. |
collection | PubMed |
description | Following central nervous system (CNS) injury, activated astrocytes form glial scars, which inhibit axonal regeneration, leading to long-term functional deficits. Engineered nanoscale scaffolds guide cell growth and enhance regeneration within models of spinal cord injury. However, the effects of micro-/nanosize scaffolds on astrocyte function are not well characterized. In this study, a high throughput (HTP) microscale platform was developed to study astrocyte cell behavior on micropatterned surfaces containing 1 μm spacing grooves with a depth of 250 or 500 nm. Significant changes in cell and nuclear elongation and alignment on patterned surfaces were observed, compared to on flat surfaces. The cytoskeleton components (particularly actin filaments and focal adhesions) and nucleus-centrosome axis were aligned along the grooved direction as well. More interestingly, astrocytes on micropatterned surfaces showed enhanced mitochondrial activity with lysosomes localized at the lamellipodia of the cells, accompanied by enhanced adenosine triphosphate (ATP) release and calcium activities. These data indicate that the lysosome-mediated ATP exocytosis and calcium signaling may play an important role in astrocytic responses to substrate topology. These new findings have furthered our understanding of the biomechanical regulation of astrocyte cell–substrate interactions, and may benefit the optimization of scaffold design for CNS healing. |
format | Online Article Text |
id | pubmed-4297955 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-42979552015-01-26 Astrocytes Increase ATP Exocytosis Mediated Calcium Signaling in Response to Microgroove Structures Singh, Ajay V. Raymond, Michael Pace, Fabiano Certo, Anthony Zuidema, Jonathan M. McKay, Christopher A. Gilbert, Ryan J. Lu, X. Lucas Wan, Leo Q. Sci Rep Article Following central nervous system (CNS) injury, activated astrocytes form glial scars, which inhibit axonal regeneration, leading to long-term functional deficits. Engineered nanoscale scaffolds guide cell growth and enhance regeneration within models of spinal cord injury. However, the effects of micro-/nanosize scaffolds on astrocyte function are not well characterized. In this study, a high throughput (HTP) microscale platform was developed to study astrocyte cell behavior on micropatterned surfaces containing 1 μm spacing grooves with a depth of 250 or 500 nm. Significant changes in cell and nuclear elongation and alignment on patterned surfaces were observed, compared to on flat surfaces. The cytoskeleton components (particularly actin filaments and focal adhesions) and nucleus-centrosome axis were aligned along the grooved direction as well. More interestingly, astrocytes on micropatterned surfaces showed enhanced mitochondrial activity with lysosomes localized at the lamellipodia of the cells, accompanied by enhanced adenosine triphosphate (ATP) release and calcium activities. These data indicate that the lysosome-mediated ATP exocytosis and calcium signaling may play an important role in astrocytic responses to substrate topology. These new findings have furthered our understanding of the biomechanical regulation of astrocyte cell–substrate interactions, and may benefit the optimization of scaffold design for CNS healing. Nature Publishing Group 2015-01-19 /pmc/articles/PMC4297955/ /pubmed/25597401 http://dx.doi.org/10.1038/srep07847 Text en Copyright © 2015, Macmillan Publishers Limited. All rights reserved http://creativecommons.org/licenses/by-nc-nd/4.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder in order to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/4.0/ |
spellingShingle | Article Singh, Ajay V. Raymond, Michael Pace, Fabiano Certo, Anthony Zuidema, Jonathan M. McKay, Christopher A. Gilbert, Ryan J. Lu, X. Lucas Wan, Leo Q. Astrocytes Increase ATP Exocytosis Mediated Calcium Signaling in Response to Microgroove Structures |
title | Astrocytes Increase ATP Exocytosis Mediated Calcium Signaling in Response to Microgroove Structures |
title_full | Astrocytes Increase ATP Exocytosis Mediated Calcium Signaling in Response to Microgroove Structures |
title_fullStr | Astrocytes Increase ATP Exocytosis Mediated Calcium Signaling in Response to Microgroove Structures |
title_full_unstemmed | Astrocytes Increase ATP Exocytosis Mediated Calcium Signaling in Response to Microgroove Structures |
title_short | Astrocytes Increase ATP Exocytosis Mediated Calcium Signaling in Response to Microgroove Structures |
title_sort | astrocytes increase atp exocytosis mediated calcium signaling in response to microgroove structures |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4297955/ https://www.ncbi.nlm.nih.gov/pubmed/25597401 http://dx.doi.org/10.1038/srep07847 |
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