Cellular Architecture Regulates Collective Calcium Signaling and Cell Contractility
AffiliationUniv Arizona, Dept Aerosp & Mech Engn
Univ Arizona, Dept Mat Sci & Engn
Univ Arizona, Dept Pharmacol & Toxicol
MetadataShow full item record
PublisherPublic Library of Science
CitationCellular Architecture Regulates Collective Calcium Signaling and Cell Contractility 2016, 12 (5):e1004955 PLOS Computational Biology
JournalPLOS Computational Biology
Rights© 2016 Sun et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
Collection InformationThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at firstname.lastname@example.org.
AbstractA key feature of multicellular systems is the ability of cells to function collectively in response to external stimuli. However, the mechanisms of intercellular cell signaling and their functional implications in diverse vascular structures are poorly understood. Using a combination of computational modeling and plasma lithography micropatterning, we investigate the roles of structural arrangement of endothelial cells in collective calcium signaling and cell contractility. Under histamine stimulation, endothelial cells in self-assembled and microengineered networks, but not individual cells and monolayers, exhibit calcium oscillations. Micropatterning, pharmacological inhibition, and computational modeling reveal that the calcium oscillation depends on the number of neighboring cells coupled via gap junctional intercellular communication, providing a mechanistic basis of the architecture-dependent calcium signaling. Furthermore, the calcium oscillation attenuates the histamine-induced cytoskeletal reorganization and cell contraction, resulting in differential cell responses in an architecture-dependent manner. Taken together, our results suggest that endothelial cells can sense and respond to chemical stimuli according to the vascular architecture via collective calcium signaling.
NoteOpen Access Journal
VersionFinal published version
SponsorsNational Institutes of Health Director's New Innovator Award [DP2OD007161]; James S. McDonnell Foundation