12 research outputs found
Analysis of protrusion dynamics in amoeboid cell motility by means of regularized contour flows
Amoeboid cell motility is essential for a wide range of biological processes including wound healing, embryonic morphogenesis, and cancer metastasis. It relies on complex dynamical patterns of cell shape changes that pose long-standing challenges to mathematical modeling and raise a need for automated and reproducible approaches to extract quantitative morphological features from image sequences. Here, we introduce a theoretical framework and a computational method for obtaining smooth representations of the spatiotemporal contour dynamics from stacks of segmented microscopy images. Based on a Gaussian process regression we propose a one-parameter family of regularized contour flows that allows us to continuously track reference points (virtual markers) between successive cell contours. We use this approach to define a coordinate system on the moving cell boundary and to represent different local geometric quantities in this frame of reference. In particular, we introduce the local marker dispersion as a measure to identify localized membrane expansions and provide a fully automated way to extract the properties of such expansions, including their area and growth time. The methods are available as an open-source software package called AmoePy, a Python-based toolbox for analyzing amoeboid cell motility (based on time-lapse microscopy data), including a graphical user interface and detailed documentation. Due to the mathematical rigor of our framework, we envision it to be of use for the development of novel cell motility models. We mainly use experimental data of the social amoeba Dictyostelium discoideum to illustrate and validate our approach
Spontaneous transitions between amoeboid and keratocyte-like modes of migration
The motility of adherent eukaryotic cells is driven by the dynamics of the
actin cytoskeleton. Despite the common force-generating actin machinery,
different cell types often show diverse modes of locomotion that differ in
their shape dynamics, speed, and persistence of motion. Recently, experiments
in Dictyostelium discoideum have revealed that different motility modes can be
induced in this model organism, depending on genetic modifications,
developmental conditions, and synthetic changes of intracellular signaling.
Here, we report experimental evidence that in a mutated D. discoideum cell line
with increased Ras activity, switches between two distinct migratory modes, the
amoeboid and fan-shaped type of locomotion, can even spontaneously occur within
the same cell. We observed and characterized repeated and reversible switchings
between the two modes of locomotion, suggesting that they are distinct
behavioral traits that coexist within the same cell. We adapted an established
phenomenological motility model that combines a reaction-diffusion system for
the intracellular dynamics with a dynamic phase field to account for our
experimental findings.Comment: Some references pointing at figures in the supplement and therefore
are not correctly displayed. The supplement is available at zenodo.or