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

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Science  29 Aug 2014:
Vol. 345, Issue 6200, pp. 1062-1065
DOI: 10.1126/science.1256965

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Push me, pull you, that's the way to move

Primary cells, derived directly from human tissue, exhibit different behaviors in shape and signaling within three-dimensional (3D) or 2D spaces. When the pressure within the cell increases, cells display limb-like bumps, which they use to move through their 3D environment. Petrie et al. now show that when the complex of actin and myosin contracts, it controls the pressure within cells and therefore the shape of those protruding structures (see the Perspective by DeSimone and Horwitz). The authors measured internal pressures in migrating mammalian cells. In the 3D matrix, those cells have higher pressure that differs between the front and back of the cell, which creates a piston effect.

Science, this issue p. 1062; see also p. 1002


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.

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