Dataset Information

Excitable actin dynamics and amoeboid cell migration.

ABSTRACT: Amoeboid cell migration is characterized by frequent changes of the direction of motion and resembles a persistent random walk on long time scales. Although it is well known that cell migration is typically driven by the actin cytoskeleton, the cause of this migratory behavior remains poorly understood. We analyze the spontaneous dynamics of actin assembly due to nucleation promoting factors, where actin filaments lead to an inactivation of these factors. We show that this system exhibits excitable dynamics and can spontaneously generate waves, which we analyze in detail. By using a phase-field approach, we show that these waves can generate cellular random walks. We explore how the characteristics of these persistent random walks depend on the parameters governing the actin-nucleator dynamics. In particular, we find that the effective diffusion constant and the persistence time depend strongly on the speed of filament assembly and the rate of nucleator inactivation. Our findings point to a deterministic origin of the random walk behavior and suggest that cells could adapt their migration pattern by modifying the pool of available actin.

SUBMITTER: Ecker N

PROVIDER: S-EPMC7850500 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Excitable actin dynamics and amoeboid cell migration.

Ecker Nicolas N Kruse Karsten K

PloS one 20210201 2

Amoeboid cell migration is characterized by frequent changes of the direction of motion and resembles a persistent random walk on long time scales. Although it is well known that cell migration is typically driven by the actin cytoskeleton, the cause of this migratory behavior remains poorly understood. We analyze the spontaneous dynamics of actin assembly due to nucleation promoting factors, where actin filaments lead to an inactivation of these factors. We show that this system exhibits excita ...[more]

PMID: 33524055

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Project description:Background: Cancer metastasis is dependent on cell migration. Several mechanisms, including epithelial-to-mesenchymal transition (EMT) and actin fiber formation, could be involved in cancer cell migration. As a downstream effector of the Hippo signaling pathway, transcriptional coactivator with PDZbinding motif (TAZ) is recognized as a key mediator of the metastatic ability of breast cancer cells. We aimed to examine whether TAZ affects the migration of breast cancer cells through the regulation of EMT or actin cytoskeleton. Methods: MCF-7 and MDA-MB-231 cells were treated with siRNA to attenuate TAZ abundance. Transwell migration assay and scratch wound healing assay were performed to study the effects of TAZ knockdown on cancer cell migration. Fluorescence microscopy was conducted to examine the vinculin and phalloidin. Semiquantitative immunoblotting and quantitative real-time PCR were performed to study the expression of small GTPases and kinases. Changes in the expression of genes associated with cell migration were examined through next-generation sequencing. Results: TAZ-siRNA treatment reduced TAZ abundance in MCF-7 and MDA-MB- 231 breast cancer cells, which was associated with a significant decrease in cell migration. TAZ knockdown increased the expression of fibronectin, but it did not exhibit the typical pattern of EMT progression. TGF-b treatment in MDA-MB-231 cells resulted in a reduction in TAZ and an increase in fibronectin levels. However, it paradoxically promoted cell migration, suggesting that EMT is unlikely to be involved in the decreased migration of breast cancer cells in response to TAZ suppression. RhoA, a small Rho GTPase protein, was significantly reduced in response to TAZ knockdown. This caused a decrease in the expression of the Rho-dependent downstream pathway, i.e., LIM kinase 1 (LIMK1), phosphorylated LIMK1/2, and phosphorylated cofilin, leading to actin depolymerization. Furthermore, myosin light chain kinase (MLCK) and phosphorylated MLC2 were significantly decreased in MDA-MB-231 cells with TAZ knockdown, inhibiting the assembly of stress fibers and focal adhesions. Conclusion: TAZ knockdown inhibits the migration of breast cancer cells by regulating the intracellular actin cytoskeletal organization. This is achieved, in part, by reducing the abundance of RhoA and Rho-dependent downstream kinase proteins, which results in actin depolymerization and the disassembly of stress fibers and focal adhesions.

Dataset Information

Excitable actin dynamics and amoeboid cell migration.

Publications

Excitable actin dynamics and amoeboid cell migration.

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