Dataset Information

Geometry-Driven Polarity in Motile Amoeboid Cells.

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.

SUBMITTER: Nagel O

PROVIDER: S-EPMC4262208 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Geometry-Driven Polarity in Motile Amoeboid Cells.

Nagel Oliver O Guven Can C Theves Matthias M Driscoll Meghan M Losert Wolfgang W Beta Carsten C

PloS one 20141210 12

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. In ...[more]

PMID: 25493548

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Project description:Dendritic cell (DC) migration is required for efficient presentation of antigen to T cells and the initiation of an adaptive immune response. In spite of its importance, many aspects of DC migration have not been characterized. DCs encounter a variety of environments with different stiffness and geometry, but the effect of these parameters on DC migration has not yet been determined. We addressed this question by comparing DC motility on standard migration surfaces (polydimethylsiloxane (PDMS)-coated coverslips) and micropost array detectors (mPADs). These two surfaces differ in both stiffness and geometry. We found that DC migration was affected by substrate type, with significant increases in speed and significant decreases in persistence time on mPADs made of PDMS as compared to spin-coated PDMS coverslips. To determine whether the geometry or compliance of the post arrays was responsible for these changes in DC migration, we quantified DC motility on mPADs of identical geometry but different stiffness. Migration was indistinguishable on these mPADs, suggesting that DCs are responsive to geometry of ligand presentation and not stiffness. Further, by micropatterning ligands on flat PDMS surfaces in similar geometries to the mPAD arrays, we determined that DCs respond to the geometry of printed ligand. Finally, we used a variety of small molecule inhibitors to identify pathways involved in geometry sensing. We saw a significant role for myosin contractility and ?5?1 integrin engagement. We also noted significant reorganization of the actin cytoskeleton into dynamic actin rings when DCs were motile on posts. From these experiments, we conclude that DCs are insensitive to substrate compliance in the range tested but respond to changes in geometry via a mechanism that involves integrin function, myosin contractility, and remodeling of the actin cytoskeleton. As a possible explanation, we postulate a consistent role for filopodial extension and contraction as the driver of DC motility.

Dataset Information

Geometry-Driven Polarity in Motile Amoeboid Cells.

Publications

Geometry-Driven Polarity in Motile Amoeboid Cells.

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