Generation of compartmentalized pressure by a nuclear piston governs cell motility in a 3D matrix

Science. 2014 Aug 29;345(6200):1062-5. doi: 10.1126/science.1256965.


Cells use actomyosin contractility to move through three-dimensional (3D) extracellular matrices. Contractility affects the type of protrusions cells use to migrate in 3D, but the mechanisms are unclear. In this work, we found that contractility generated high-pressure lobopodial protrusions in human cells migrating in a 3D matrix. In these cells, the nucleus physically divided the cytoplasm into forward and rear compartments. Actomyosin contractility with the nucleoskeleton-intermediate filament linker protein nesprin-3 pulled the nucleus forward and pressurized the front of the cell. Reducing expression of nesprin-3 decreased and equalized the intracellular pressure. Thus, the nucleus can act as a piston that physically compartmentalizes the cytoplasm and increases the hydrostatic pressure between the nucleus and the leading edge of the cell to drive lamellipodia-independent 3D cell migration.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Actomyosin / physiology
  • Cell Movement / physiology*
  • Cell Nucleus / physiology*
  • Cells, Cultured
  • Cytoplasm / physiology
  • Extracellular Matrix / physiology*
  • Extracellular Matrix / ultrastructure
  • Fibroblasts / physiology*
  • Humans
  • Hydrostatic Pressure
  • Microfilament Proteins
  • Pseudopodia / physiology*
  • Vimentin / metabolism


  • Microfilament Proteins
  • SYNE3 protein, human
  • Vimentin
  • Actomyosin