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

Cell Rep. 2019 May 7;27(6):1897-1909.e4. doi: 10.1016/j.celrep.2019.04.035.


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.

Keywords: actin cytoskeleton; cell memory; cell migration; cell shape; cell spreading; cell-matrix adhesion; cellular Potts model; mathematical modeling; mechanobiology; stress fibers.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actin Cytoskeleton / drug effects
  • Actin Cytoskeleton / metabolism
  • Cell Adhesion / drug effects
  • Cell Line, Tumor
  • Cell Movement* / drug effects
  • Collagen / metabolism
  • Computer Simulation
  • Extracellular Matrix / drug effects
  • Extracellular Matrix / metabolism*
  • Half-Life
  • Heterocyclic Compounds, 4 or More Rings / pharmacology
  • Humans
  • Kinetics
  • Models, Biological
  • Pseudopodia / drug effects
  • Pseudopodia / metabolism
  • Stress Fibers / drug effects
  • Stress Fibers / metabolism*
  • Time Factors


  • Heterocyclic Compounds, 4 or More Rings
  • blebbistatin
  • Collagen