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Title: Three-dimensional model of intracellular and intercellular Ca2+ waves propagation in endothelial cells

Journal Article · · Biochemical and Biophysical Research Communications
 [1]; ;  [2];  [3];  [4];  [1]
  1. Department of Mechanical Engineering, Faculty of Engineering, Kyushu University (Japan)
  2. Department of Mechanical Engineering, Graduate School of Engineering, Kyushu University (Japan)
  3. Advanced Center for Computing and Communication, RIKEN (Japan)
  4. Image Processing Research Team, RIKEN Center for Advanced Photonics, RIKEN (Japan)

Highlights: • Image-based 3D simulation model for intercellular and intracellular Ca{sup 2+} waves. • Metabolic reactions were divided into membrane and cytoplasm domains. • Ca{sup 2+} and IP{sub 3} diffused across the cell and gap junctions. • Ca{sup 2+} waves are propagated from focal stimulated point in numerical simulation. • Ca{sup 2+} wave speed was in agreement with those from cell culture experiments. Intracellular and intercellular Ca{sup 2+} waves play key roles in cellular functions, and focal stimulation triggers Ca{sup 2+} wave propagation from stimulation points to neighboring cells, involving localized metabolism reactions and specific diffusion processes. Among these, inositol 1,4,5-trisphosphate (IP{sub 3}) is produced at membranes and diffuses into the cytoplasm to release Ca{sup 2+} from endoplasmic reticulum (ER). In this study, we developed a three-dimensional (3D) simulation model for intercellular and intracellular Ca{sup 2+} waves in endothelial cells (ECs). 3D model of 2 cells was reconstructed from confocal microscopic images and was connected via gap junctions. Cells have membrane and cytoplasm domains, and metabolic reactions were divided into each domain. Finally, the intracellular and intercellular Ca{sup 2+} wave propagations were induced using microscopic stimulation and were compared between numerical simulations and experiments. The experiments showed that initial sharp increases in intracellular Ca{sup 2+} occurred approximately 0.3 s after application of stimuli. In addition, Ca{sup 2+} wave speeds remained constant in cells, with intracellular and intercellular speeds of approximately 35 and 15 μm/s, respectively. Simulations indicated initial increases in Ca{sup 2+} concentrations at points of stimulation, and these were then propagated across stimulated and neighboring cells. In particular, initial rapid increases in intracellular Ca{sup 2+} were delayed and subsequent intracellular and intercellular Ca{sup 2+} wave speeds were approximately 25 and 12 μm/s, respectively. Simulation results were in agreement with those from cell culture experiments, indicating the utility of our 3D model for investigations of intracellular and intercellular messaging in ECs.

OSTI ID:
23107763
Journal Information:
Biochemical and Biophysical Research Communications, Vol. 505, Issue 3; Other Information: Copyright (c) 2018 Elsevier Inc. All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
Country of Publication:
United States
Language:
English

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