Three-component contour dynamics model to simulate and analyze amoeboid cell motility

TL;DR

This paper introduces a three-component mathematical model for simulating amoeboid cell motility, capturing shape changes and movement patterns, and enabling classification of cell behavior based on contour dynamics.

Contribution

The novel model combines stochastic protrusions and deterministic shape retractions, providing a simple, fast, and effective way to simulate and analyze amoeboid cell movement.

Findings

Model generates realistic cell contour data matching experimental observations.

Protrusion component correlates with actin concentration and local membrane motion.

Parameter estimation is efficient, facilitating cell behavior classification.

Abstract

Amoeboid cell motility is relevant in a wide variety of biomedical applications such as wound healing, cancer metastasis, and embryonic morphogenesis. It is characterized by pronounced changes of the cell shape associated with expansions and retractions of the cell membrane, which result in a crawling kind of locomotion. Despite existing computational models of amoeboid motion, the inference of expansion and retraction components of individual cells, the corresponding classification of cells, and the a priori specification of the parameter regime to achieve a specific motility behavior remain challenging open problems. We propose a novel model of the spatio-temporal evolution of two-dimensional cell contours comprising three biophysiologically motivated components: a stochastic term accounting for membrane protrusions and two deterministic terms accounting for membrane retractions by regularizing the shape and area of the contour. Mathematically, these correspond to the intensity of a self-exciting Poisson point process, the area-preserving curve-shortening flow, and an area adjustment flow. The model is used to generate contour data for a variety of qualitatively different, e.g., polarized and non-polarized, cell tracks that are hardly distinguishable from experimental data. In application to experimental cell tracks, we inferred the protrusion component and examined its correlation to commonly used biomarkers: the actin concentration close to the membrane and its local motion. Due to the low model complexity, parameter estimation is fast, straightforward and offers a simple way to classify contour dynamics based on two locomotion types: the amoeboid and a so-called fan-shaped type. For both types, we use cell tracks segmented from fluorescence imaging data of the model organism D. discoideum. An implementation of the model is provided within the open-source software package AmoePy.