Cortical Factor Feedback Model for Cellular Locomotion and Cytofission

TL;DR

This paper presents a cortical factor feedback model explaining various spontaneous cell movements and divisions through a positive feedback mechanism regulating actin polymerization and cellular polarity.

Contribution

It introduces a unified hypothesis that cortical factors and their feedback regulate diverse cell motility modes and cytofission, supported by stochastic simulations.

Findings

Positive feedback stabilizes or destabilizes cell movement modes.

Cell migration patterns depend on actin network formation rates.

Model predicts movement pattern changes with actin polymerization thresholds.

Abstract

Eukaryotic cells can move spontaneously without being guided by external cues. For such spontaneous movements, a variety of different modes have been observed, including the amoeboid-like locomotion with protrusion of multiple pseudopods, the keratocyte-like locomotion with a widely spread lamellipodium, cell division with two daughter cells crawling in opposite directions, and fragmentations of a cell to multiple pieces. Mutagenesis studies have revealed that cells exhibit these modes depending on which genes are deficient, suggesting that seemingly different modes are the manifestation of a common mechanism to regulate cell motion. In this paper, we propose a hypothesis that the positive feedback mechanism working through the inhomogeneous distribution of regulatory proteins underlies this variety of cell locomotion and cytofission. In this hypothesis, a set of regulatory proteins, which we call cortical factors, suppress actin polymerization. These suppressing factors are diluted at the extending front and accumulated at the retracting rear of cell, which establishes a cellular polarity and enhances the cell motility, leading to the further accumulation of cortical factors at the rear. Stochastic simulation of cell movement shows that the positive feedback mechanism of cortical factors stabilizes or destabilizes modes of movement and determines the cell migration pattern. The model predicts that the pattern is selected by changing the rate of formation of the actin-filament network or the threshold to initiate the network formation.