Wave patterns organize cellular protrusions and control cortical dynamics

Yuchuan Miao, Sayak Bhattacharya, Tatsat Banerjee, Bedri Abubaker-Sharif, Yu Long, Takanari Inoue, Pablo A. Iglesias, Peter N. Devreotes

Research output: Contribution to journalArticlepeer-review

16 Scopus citations


Cellular protrusions are typically considered as distinct structures associated with specific regulators. However, we found that these regulators coordinately localize as propagating cortical waves, suggesting a common underlying mechanism. These molecular events fell into two excitable networks, the signal transduction network STEN and the cytoskeletal network CEN with different wave substructures. Computational studies using a coupled-network model reproduced these features and showed that the morphology and kinetics of the waves depended on strengths of feedback loops. Chemically induced dimerization at multiple nodes produced distinct, coordinated alterations in patterns of other network components. Taken together, these studies indicate: STEN positive feedback is mediated by mutual inhibition between Ras/Rap and PIP2, while negative feedback depends on delayed PKB activation; PKBs link STEN to CEN; CEN includes positive feedback between Rac and F-actin, and exerts fast positive and slow negative feedbacks to STEN. The alterations produced protrusions resembling filopodia, ruffles, pseudopodia, or lamellipodia, suggesting that these structures arise from a common regulatory mechanism and that the overall state of the STEN-CEN system determines cellular morphology.

Original languageEnglish (US)
Article numbere8585
JournalMolecular systems biology
Issue number3
StatePublished - Mar 2019


  • cell migration
  • cellular protrusion
  • complex network
  • excitable system
  • pattern formation

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Information Systems
  • Applied Mathematics
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Computational Theory and Mathematics


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