Extracellular Matrix Geometry and Initial Adhesive Position Determine Stress Fiber Network Organization during Cell Spreading

Summary: Three-dimensional matrices often contain highly structured adhesive tracks that require cells to turn corners and bridge non-adhesive areas. Here, we investigate these complex processes using micropatterned cell adhesive frames. Spreading kinetics on these matrices depend strongly on initial adhesive position and are predicted by a cellular Potts model (CPM), which reflects a balance between adhesion and intracellular tension. As cells spread, new stress fibers (SFs) assemble periodically and parallel to the leading edge, with spatial intervals of ∼2.5 μm, temporal intervals of ∼15 min, and characteristic lifetimes of ∼50 min. By incorporating these rules into the CPM, we can successfully predict SF network architecture. Moreover, we observe broadly similar behavior when we culture cells on arrays of discrete collagen fibers. Our findings show that ECM geometry and initial cell position strongly determine cell spreading and that cells encode a memory of their spreading history through SF network organization. : Kassianidou et al. use adhesive micropatterns to recapitulate features of 3D extracellular matrices and to integrate live-cell imaging with mathematical modeling. They find that spreading trajectories are determined by a balance between adhesion energy, surface tension, and line tension, and that cells produce a stress fiber network that encodes the spreading history. Keywords: cell-matrix adhesion, cell shape, cell spreading, actin cytoskeleton, stress fibers, mathematical modeling, cellular Potts model, cell memory, mechanobiology, cell migration