Fittings of the model to the experimental data.

<p>(A) GA-treated, and (B) control data sets with dashed lines representing the data in dimensionless NF units and solid lines representing the model simulations with arbitrary units representing [Ca^<b>2+</b>]_i in μM concentrations. The uppermost curve pair (blue) represents NB1, the second uppermost NB2 (green), followed by NB3 (red), NB4 (light blue), NB5 (purple), NB6 (yellow), NB7 (black), NB8 (light red), NB9 (grey), and NB10 (orange).</p

Kinetic diagram.

<p>Kinetics of the model component I (SSCC) were combined with the kinetics of model components II-IV from the original models of the P₂Y₂ receptor[<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0128434#pone.0128434.ref021" target="_blank">21</a>], IP₃R₃[<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0128434#pone.0128434.ref022" target="_blank">22</a>], and RyR[<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0128434#pone.0128434.ref023" target="_blank">23</a>].</p

Fittings of the model to the experimental data.

<p>(A) GA-treated, and (B) control data sets with dashed lines representing the data in dimensionless NF units and solid lines representing the model simulations with arbitrary units representing [Ca^<b>2+</b>]_i in μM concentrations. The uppermost curve pair (blue) represents NB1, the second uppermost NB2 (green), followed by NB3 (red), NB4 (light blue), NB5 (purple), NB6 (yellow), NB7 (black), NB8 (light red), NB9 (grey), and NB10 (orange).</p

Schematic diagram of the Ca²⁺ signaling model.

<p>Solid arrows represent Ca^<b>2+</b> fluxes and dashed arrows IP₃ dynamics. Roman numerals denote the model components I-VI. Abbreviations: [Ca^<b>2+</b>]_i = cytoplasmic Ca^<b>2+</b> concentration, [L] = extracellular ligand concentration, [IP₃] = cytoplasmic IP₃ concentration, SSCC = stretch-sensitive Ca^<b>2+</b> channel, P₂Y₂ = purinergic receptor type P₂Y₂, IP₃R₃ = IP₃ receptor type 3, RyR = ryanodine receptor, SERCA = sarco/endoplasmic reticulum Ca^<b>2+</b> ATPase, PMCA = plasma membrane Ca^<b>2+</b> ATPase, Leak = combinatory Ca^<b>2+</b> leak from the extracellular space and the endoplasmic reticulum (ER), GJ = gap junction, ϕ = degradation.</p

Constant parameters and initial conditions.

<p>Most of the parameters were taken from the models of Lemon et al. 2003[<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0128434#pone.0128434.ref021" target="_blank">21</a>] for P₂Y₂ receptor, LeBeau et al. 1999[<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0128434#pone.0128434.ref022" target="_blank">22</a>] for IP₃R₃, and Keizer & Levine 1996[<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0128434#pone.0128434.ref023" target="_blank">23</a>] for RyR. Reference ‘fitted’ means that the parameter was optimized in this study.</p><p>Constant parameters and initial conditions.</p

Polarization of the ARPE-19 monolayer.

<p>Z-projections (XZ and YZ) from apical side to basal side and maximum intensity projection of the XY plane in the ARPE-19 monolayer represent the localization of Zonula Occludens (ZO-1, red) in the confocal micrograph after immunofluorescence labeling with the nuclear label 4’,6-diamidino-2-phenylindole (DAPI, blue). Scale bar is 10μm.</p

R² values indicating the goodness of fit between the model and the data.

<p>R² values are listed separately for each data set and NB layer.</p><p>R² values indicating the goodness of fit between the model and the data.</p

Numbering of the cell layers.

<p>Schematic representation of the location of the mechanically stimulated (MS) cell with respect to the neighboring (NB) cell layers: NB₁ is the first layer which is in direct contact with the MS cell; NB₂ is the second layer which is in direct contact with NB₁, and so forth. White line segment marks an apothem (a) of a hexagon.</p