Directed migration of cancer cells guided by the graded texture of the underlying matrix

Jin Seok Park, Deok Ho Kim, Hong Nam Kim, Chiaochun Joanne Wang, Moon Kyu Kwak, Eunmi Hur, Kahp Yang Suh, Steven S. An, Andre Levchenko

Research output: Contribution to journalArticlepeer-review

Abstract

Living cells and the extracellular matrix (ECM) can exhibit complex interactions that define key developmental, physiological and pathological processes. Here, we report a new type of directed migration - which we term 'topotaxis' - guided by the gradient of the nanoscale topographic features in the cells' ECM environment. We show that the direction of topotaxis is reflective of the effective cell stiffness, and that it depends on the balance of the ECM-triggered signalling pathways PI(3)K-Akt and ROCK-MLCK. In melanoma cancer cells, this balance can be altered by different ECM inputs, pharmacological perturbations or genetic alterations, particularly a loss of PTEN in aggressive melanoma cells. We conclude that topotaxis is a product of the material properties of cells and the surrounding ECM, and propose that the invasive capacity of many cancers may depend broadly on topotactic responses, providing a potentially attractive mechanism for controlling invasive and metastatic behaviour.

Original languageEnglish (US)
Pages (from-to)792-801
Number of pages10
JournalNature Materials
Volume15
Issue number7
DOIs
StatePublished - Jul 1 2016

ASJC Scopus subject areas

  • Chemistry(all)
  • Materials Science(all)
  • Condensed Matter Physics
  • Mechanics of Materials
  • Mechanical Engineering

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