title: Cellular Architecture Regulates Collective Calcium Signaling and Cell Contractility.
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.
authors.affiliation: Department of Mechanical Science and Engineering, University of Illinois at Urbana-Champaign, Urbana, Illinois, United States of America.|Department of Aerospace and Mechanical Engineering, The University of Arizona, Tucson, Arizona, United States of America.
authors.forename: Jian
authors.identifier: 0000-0001-8539-6590
authors.initials: J
authors.lastname: Sun
authors.affiliation: Cardiovascular Innovation Institute, University of Louisville & Jewish Hospital, Louisville, Kentucky, United States of America.
authors.forename: James B
authors.initials: JB
authors.lastname: Hoying
authors.affiliation: Material Science and Engineering Department, The University of Arizona, Tucson, Arizona, United States of America.
authors.forename: Pierre A
authors.initials: PA
authors.lastname: Deymier
authors.affiliation: Department of Pharmacology and Toxicology, The University of Arizona, Tucson, Arizona, United States of America.
authors.forename: Donna D
authors.initials: DD
authors.lastname: Zhang
authors.affiliation: Department of Aerospace and Mechanical Engineering, The University of Arizona, Tucson, Arizona, United States of America.|Departments of Biomedical Engineering, Mechanical Engineering, and Surgery, The Pennsylvania State University, University Park, Pennsylvania, United States of America.
authors.forename: Pak Kin
authors.initials: PK
authors.lastname: Wong
mesh_terms: D008841:Actin Cytoskeleton / Q000187:drug effects / Q000502:physiology; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology*; D002450:Cell Communication / Q000187:drug effects / Q000502:physiology; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D060833:Cellular Microenvironment / Q000187:drug effects / Q000502:physiology; D019295:Computational Biology; D003198:Computer Simulation; D042783:Endothelial Cells / Q000187:drug effects / Q000502:physiology; D017629:Gap Junctions / Q000187:drug effects / Q000502:physiology; D006632:Histamine / Q000494:pharmacology; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D008954:Models, Biological
chemical_list: D006632:Histamine