. Taking together, this can clearly justify how electrotaxis is the most

. Taking together, this can clearly justify how electrotaxis is the most effective guiding mechanism of the cell elongation, CMI and the cell RI, which dominates other effective cues during cell motility, reported in many experimental works [6, 38, 110]. In summary, this study characterizes, for the first time, cell shape change accompanied with the cell migration change within 3D multi-signaling environments. We believe that it provides one step forward in computational methodology to simultaneously consider different features of cell Citarinostat biological activity behavior which are a concern in various biological processes. Although more sophisticated experimental works are required to calibrate quantitatively the present model, general aspects of the results discussed here are qualitatively consistent with documented experimental findings.Supporting InformationS1 Video. Shape changes during cell migration within a substrate with a linear stiffness gradient. The substrate stiffness changes linearly in x direction from 1 kPa at x = 0 to 100 kPa atPLOS ONE | DOI:10.1371/journal.pone.0122094 March 30,26 /3D Num. Model of Cell Morphology during Mig. in Multi-Signaling Sub.x = 400 m. At the beginning the cell is located in the soft region. The results demonstrate that the cell migrates in the direction of stiffness gradient and the cell centroid finally moves around an IEP located at x = 351 ?5 m. (AVI) S2 Video. Shape changes during cell migration within a substrate with conjugate linear stiffness and thermal gradients (th = 0.2). It is assumed that there is a linear thermal gradient in x direction (as stiffness gradient) which changes from 36 at x = 0 to 39 at x = 400 m. At the beginning the cell is located near the surface with lower temperature. The results demonstrate that the cell migrates along the thermal gradient towards warmer region. Finally, the cell centroid moves around an IEP located at x = 359 ?3 m. When the cell centroid is near the IEP the cell may send out and retract protrusions but it maintains the position around IEP. (AVI) S3 Video. Shape changes during cell migration in presence of (-)-Blebbistatin site chemotaxis (ch = 0.35) 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 near the surface of null chemoattractant substance. The results demonstrate that, the cell migrates along the chemical gradient towards the higher chemoattractant concentration. In this case, the cell centroid finally keeps moving around an IEP located at x = 368 ?3 m. The ultimate position of IEP is sensitive to the chemical effective factor. (AVI) S4 Video. Shape changes during cell migration in presence of chemotaxis (ch = 0.40) 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 near the surface of null chemoattractant substance. The results demonstrate that, the cell migrates along the chemical gradient towards the higher chemoattractant concentration. For higher chemical effective factor, ch = 0.4, the position of the IEP moves towards chemoattractant source to locate at at x = 374 ?4 m. (AVI) S5 Video. Shape changes during cell migration in presence of electrotaxis within a substrate with stiffness gradient. A ce.. Taking together, this can clearly justify how electrotaxis is the most effective guiding mechanism of the cell elongation, CMI and the cell RI, which dominates other effective cues during cell motility, reported in many experimental works [6, 38, 110]. In summary, this study characterizes, for the first time, cell shape change accompanied with the cell migration change within 3D multi-signaling environments. We believe that it provides one step forward in computational methodology to simultaneously consider different features of cell behavior which are a concern in various biological processes. Although more sophisticated experimental works are required to calibrate quantitatively the present model, general aspects of the results discussed here are qualitatively consistent with documented experimental findings.Supporting InformationS1 Video. Shape changes during cell migration within a substrate with a linear stiffness gradient. The substrate stiffness changes linearly in x direction from 1 kPa at x = 0 to 100 kPa atPLOS ONE | DOI:10.1371/journal.pone.0122094 March 30,26 /3D Num. Model of Cell Morphology during Mig. in Multi-Signaling Sub.x = 400 m. At the beginning the cell is located in the soft region. The results demonstrate that the cell migrates in the direction of stiffness gradient and the cell centroid finally moves around an IEP located at x = 351 ?5 m. (AVI) S2 Video. Shape changes during cell migration within a substrate with conjugate linear stiffness and thermal gradients (th = 0.2). It is assumed that there is a linear thermal gradient in x direction (as stiffness gradient) which changes from 36 at x = 0 to 39 at x = 400 m. At the beginning the cell is located near the surface with lower temperature. The results demonstrate that the cell migrates along the thermal gradient towards warmer region. Finally, the cell centroid moves around an IEP located at x = 359 ?3 m. When the cell centroid is near the IEP the cell may send out and retract protrusions but it maintains the position around IEP. (AVI) S3 Video. Shape changes during cell migration in presence of chemotaxis (ch = 0.35) 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 near the surface of null chemoattractant substance. The results demonstrate that, the cell migrates along the chemical gradient towards the higher chemoattractant concentration. In this case, the cell centroid finally keeps moving around an IEP located at x = 368 ?3 m. The ultimate position of IEP is sensitive to the chemical effective factor. (AVI) S4 Video. Shape changes during cell migration in presence of chemotaxis (ch = 0.40) 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 near the surface of null chemoattractant substance. The results demonstrate that, the cell migrates along the chemical gradient towards the higher chemoattractant concentration. For higher chemical effective factor, ch = 0.4, the position of the IEP moves towards chemoattractant source to locate at at x = 374 ?4 m. (AVI) S5 Video. Shape changes during cell migration in presence of electrotaxis within a substrate with stiffness gradient. A ce.