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Title: Cellular Architecture Regulates Collective Calcium Signaling and Cell Contractility.

Authors: Sun, Jian; Hoying, James B; Deymier, Pierre A; Zhang, Donna D; Wong, Pak Kin

Published In PLoS Comput Biol, (2016 05)

Abstract: A 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.

PubMed ID: 27196735 Exiting the NIEHS site

MeSH Terms: Actin Cytoskeleton/drug effects; Actin Cytoskeleton/physiology; Calcium Signaling/drug effects; Calcium Signaling/physiology*; Cell Communication/drug effects; Cell Communication/physiology; Cell Movement/drug effects; Cell Movement/physiology*; Cellular Microenvironment/drug effects; Cellular Microenvironment/physiology; Computational Biology; Computer Simulation; Endothelial Cells/drug effects; Endothelial Cells/physiology; Gap Junctions/drug effects; Gap Junctions/physiology; Histamine/pharmacology; Human Umbilical Vein Endothelial Cells; Humans; Models, Biological

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