Shin I. Nishimura

Cortical Factor Feedback Model for Cellular Locomotion and Cytofission

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.

Chemotaxis of a eukaryotic cell in complex gradients of chemoattractants

We studied the chemotaxis of a eukaryotic cell by constructing a mathematical model that takes into account chemical kinetics as well as the cellular shape. A cell is defined as a single domain on discrete two-dimensional grids. In the cellular domain each grid contains three kinds of molecule, an activator and inhibitor of the actin polymerization, and polymerized actins. The external signal promotes production of both activator and inhibitor and thus changes the amount of polymerized actins. If the amount of polymerized actins in a grid of the cell border (i.e., the cellular membrane) is larger than a certain threshold, then a new grid adjacent to the border is assigned to the cellular grid. Upon this change of the cellular shape, constraints are imposed to preserve the cellular volume and to make the length of the cellular border as small as possible. The cell moves in the grid space driven by this change of the cellular shape. We succeeded in reproducing chemotaxis in a linear gradient. For two more complex gradients, the behavior of our cell is consistent with experimental results.