Animal cells move around within the 3D environment of tissues during development, immune surveillance or to spread cancer. However, the cells’ diameter is often larger than that of the pores they face. Some cells—such as epithelial cells—use enzymes to remove cells and extracellular matrix blocking their way. It is less clear how amoeboid cells, such as leukocytes of the immune system, travel, as they do not use this mechanism. Michael Sixt and colleagues report that to select the path of least resistance, leukocytes make use of their largest compartment—the nucleus—to mechanically gauge suitable pores while cytoplasmic protrusions explore smaller pores. Once the cell ‘finds’ that this bulky organelle coupled to the cell’s microtubule-organizing centre fits into a pore, it retracts the more malleable cytoplasmic protrusions using microtubules and proceeds through the larger pore.
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