Abstract
Motile eukaryotic cells, such as leukocytes, cancer cells, and amoeba, typically move inside the narrow interstitial spacings of tissue or soil. While most of our knowledge of actin-driven eukaryotic motility was obtained from cells that move on planar open surfaces, recent work has demonstrated that confinement can lead to strongly altered motile behavior. Here, we report experimental evidence that motile amoeboid cells undergo a spontaneous symmetry breaking in confined interstitial spaces. Inside narrow channels, the cells switch to a highly persistent, unidirectional mode of motion, moving at a constant speed along the channel. They remain in contact with the two opposing channel side walls and alternate protrusions of their leading edge near each wall. Their actin cytoskeleton exhibits a characteristic arrangement that is dominated by dense, stationary actin foci at the side walls, in conjunction with less dense dynamic regions at the leading edge. Our experimental findings can be explained based on an excitable network model that accounts for the confinement-induced symmetry breaking and correctly recovers the spatio-temporal pattern of protrusions at the leading edge. Since motile cells typically live in the narrow interstitial spacings of tissue or soil, we expect that the geometry-driven polarity we report here plays an important role for movement of cells in their natural environment.
Highlights
Many essential biological processes rely on the ability of eukaryotic cells to move [1]
Our experimental findings show that motile amoeboid cells can undergo a spontaneous symmetry breaking under the influence of mechanical confinement
Dense actin-rich regions are observed in contact areas with the side walls and a less dense dynamic region of polymerizing actin mediates the formation of protrusions at the leading edge
Summary
Many essential biological processes rely on the ability of eukaryotic cells to move [1]. Prominent examples are embryonic development, immune responses, and the spreading of metastatic cancer cells. Geometry-Driven Polarity amoeboid motion, protrusions are formed at the leading edge by actin polymerization against the cell membrane, while the contractile action of myosin II retracts the rear of the cell body. The asymmetric distribution of cytoskeletal components and their associated forces are hallmarks of cell polarity, typically associated with an asymmetric morphology and a polar distribution of other subcellular components like signaling proteins and membrane lipids [4]. During eukaryotic gradient sensing, cells detect concentration differences of chemoattractants across their cell body and respond by asymmetrical redistribution of intracellular signaling components. The asymmetric signaling pattern triggers a polar rearrangement of the actin cortex that results in directed chemotactic movement towards the source of the chemoattractant [5]
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