Ient. It is QVD-OPH site assumed that a chemoattractant substance with concentration of 5?0-5 M exists at x = 400 m while chemoattractant concentration at x = 0 m is null. This creates a linear chemical gradient along the x axis. The evolution of shape changes during cell migration in the JNJ-26481585 web presence of chemotaxis is presented in Fig 11 for two different chemotaxis effective factors, ch = 0.35 and ch = 0.4. In Fig 6, the trajectory, which is tracked by the cell centroid, is compared with that of the previous experiments. It implies that the cell centroid ultimately moves around an IEP located at x = 368 ?3 m and x = 374 ?4 m for ch = 0.35 and ch = 0.4, respectively, (Fig 8). Therefore, it can be deduced that adding a chemotactic stimulus to the substrate moves the final position of the cell centroid towards the chemoattractant source, of course depending on the employed chemotactic effective factor. SimilarFig 10. Cell elongation, elong (left axis), and CMI (right axis) versus the cell centroid translocation in the presence of thermotaxis. The cell elongation and CMI are maximum in the intermediate regions of the substrate and decreases as the cell approaches the unconstrained surface with higher temperature. doi:10.1371/journal.pone.0122094.gPLOS ONE | DOI:10.1371/journal.pone.0122094 March 30,18 /3D Num. Model of Cell Morphology during Mig. in Multi-Signaling Sub.Fig 11. Shape changes during cell migration in presence of chemotaxis within a substrate with stiffness gradient. It is assumed that there is a chemoattractant substance with concentration of 5?0-5 M at x = 400 m, which creates a linear chemical gradient across x direction. At the beginning the cell is located at one of the corners of the substrate near the surface of null chemoattractant substance. Two chemotaxis effective factors are considered; ch = 0.35 (a and b) and ch = 0.4 (c and d). The results demonstrate that, for both cases, the cell migrates along the chemical gradient towards the higher chemoattractant concentration. Depending on chemical effective factor, the ultimate position of the cell centroid will be different, for ch = 0.35 the cellPLOS ONE | DOI:10.1371/journal.pone.0122094 March 30,19 /3D Num. Model of Cell Morphology during Mig. in Multi-Signaling Sub.centroid keeps moving around an IEP located at x = 368 ?3 m (b) while for higher chemical effective factor, ch = 0.4, the position of the IEP moves towards chemoattractant source to locate at x = 374 ?4 m (d). It is remarkable that in both cases the IEP displaces further towards the end of substrate in comparison with thermotaxis case (see also S3 and S4 Videos for low and high chemical effective factors, respectively). doi:10.1371/journal.pone.0122094.gbehavior of cell motility has been observed in the previously presented work by the same authors in which the cell has been represented by a constant spherical shape [67]. In both cases, when the cell is near to the chemoattractant source, it may extend or retract protrusions in random directions, no cell tendency to leave the IEP. It is clear from Fig 12 that for both cases the cell follows the same trend as that of the previous examples in terms of the cell elongation and CMI. However, here, the peak of the cell elongation and CMI slightly increases in comparison with mechanotaxis and/or thermotaxis. In the presence of chemotaxis, the cell tends to spread on the surface on which chemoattractant source is located. It causes cell elongation and CMI increase in perpendicula.Ient. It is assumed that a chemoattractant substance with concentration of 5?0-5 M exists at x = 400 m while chemoattractant concentration at x = 0 m is null. This creates a linear chemical gradient along the x axis. The evolution of shape changes during cell migration in the presence of chemotaxis is presented in Fig 11 for two different chemotaxis effective factors, ch = 0.35 and ch = 0.4. In Fig 6, the trajectory, which is tracked by the cell centroid, is compared with that of the previous experiments. It implies that the cell centroid ultimately moves around an IEP located at x = 368 ?3 m and x = 374 ?4 m for ch = 0.35 and ch = 0.4, respectively, (Fig 8). Therefore, it can be deduced that adding a chemotactic stimulus to the substrate moves the final position of the cell centroid towards the chemoattractant source, of course depending on the employed chemotactic effective factor. SimilarFig 10. Cell elongation, elong (left axis), and CMI (right axis) versus the cell centroid translocation in the presence of thermotaxis. The cell elongation and CMI are maximum in the intermediate regions of the substrate and decreases as the cell approaches the unconstrained surface with higher temperature. doi:10.1371/journal.pone.0122094.gPLOS ONE | DOI:10.1371/journal.pone.0122094 March 30,18 /3D Num. Model of Cell Morphology during Mig. in Multi-Signaling Sub.Fig 11. Shape changes during cell migration in presence of chemotaxis within a substrate with stiffness gradient. It is assumed that there is a chemoattractant substance with concentration of 5?0-5 M at x = 400 m, which creates a linear chemical gradient across x direction. At the beginning the cell is located at one of the corners of the substrate near the surface of null chemoattractant substance. Two chemotaxis effective factors are considered; ch = 0.35 (a and b) and ch = 0.4 (c and d). The results demonstrate that, for both cases, the cell migrates along the chemical gradient towards the higher chemoattractant concentration. Depending on chemical effective factor, the ultimate position of the cell centroid will be different, for ch = 0.35 the cellPLOS ONE | DOI:10.1371/journal.pone.0122094 March 30,19 /3D Num. Model of Cell Morphology during Mig. in Multi-Signaling Sub.centroid keeps moving around an IEP located at x = 368 ?3 m (b) while for higher chemical effective factor, ch = 0.4, the position of the IEP moves towards chemoattractant source to locate at x = 374 ?4 m (d). It is remarkable that in both cases the IEP displaces further towards the end of substrate in comparison with thermotaxis case (see also S3 and S4 Videos for low and high chemical effective factors, respectively). doi:10.1371/journal.pone.0122094.gbehavior of cell motility has been observed in the previously presented work by the same authors in which the cell has been represented by a constant spherical shape [67]. In both cases, when the cell is near to the chemoattractant source, it may extend or retract protrusions in random directions, no cell tendency to leave the IEP. It is clear from Fig 12 that for both cases the cell follows the same trend as that of the previous examples in terms of the cell elongation and CMI. However, here, the peak of the cell elongation and CMI slightly increases in comparison with mechanotaxis and/or thermotaxis. In the presence of chemotaxis, the cell tends to spread on the surface on which chemoattractant source is located. It causes cell elongation and CMI increase in perpendicula.