Figure 4. Overview of cell spreading and orientation under cyclic stretch conditions.

Spreading of fibroblasts upon CTS application occurs in two phases. In the first phase (“Spreading”) the initial cell attachment is generated. Then a circular lamellipodia and dot-like cell-matrix adhesion sites are visible. The cell reaches its critical adhesive area. In the beginning of the second phase (“Polarization/Orientation”) the cell adhesive area reaches its maximum and cell elongation is initiated. The cell develops with increasing time of stretching pronounced actin stress fibers and cell-matrix adhesions which become with time perpendicularly oriented with respect to the stretch axis. In the spreading phase the formation of actin bundles in parallel to the stretch axis is observed while cell-matrix adhesions emerged homogenously distributed along the cell edges independently of the stretch direction. Cell-matrix adhesions sites reoriented into a perpendicular alignment and the parallel actin fibers realign into a perpendicular orientation and partially disassemble as the stretching force continues to act on the cell.