Abstract

Eukaryotic cells extend pseudopodia for movement. In the absence of external cues, cells move in random directions, but with a strong element of persistence that keeps them moving in the same direction Persistence allows cells to disperse over larger areas and is instrumental to enter new environments where spatial cues can lead the cell. Here we explore cell movement by analyzing the direction, size and timing of ∼2000 pseudopodia that are extended by Dictyostelium cells. The results show that pseudpopod are extended perpendicular to the surface curvature at the place where they emerge. The location of new pseudopods is not random but highly ordered. Two types of pseudopodia may be formed: frequent splitting of an existing pseudopod, or the occasional extension of a de novo pseudopod at regions devoid of recent pseudopod activity. Split-pseudopodia are extended at ∼60 degrees relative to the previous pseudopod, mostly as alternating Right/Left/Right steps leading to relatively straight zigzag runs. De novo pseudopodia are extended in nearly random directions thereby interrupting the zigzag runs. Persistence of cell movement is based on the ratio of split versus de novo pseudopodia. We identify PLA2 and cGMP signaling pathways that modulate this ratio of splitting and de novo pseudopodia, and thereby regulate the dispersal of cells. The observed ordered extension of pseudopodia in the absence of external cues provides a fundamental insight into the coordinated movement of cells, and might form the basis for movement that is directed by internal or external cues.

Highlights

  • The movement of amoeboid cells is mediated by actin-filled protrusions of the cell surface, pseudopodia [1]

  • The cells may extend pseudopodia from areas of the cell not previously active, which we describe as de novo pseudopodia

  • The de novo pseudopodia often start as slender extensions that become wider as they incorporate the cell body (Fig. 1A)

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Summary

Introduction

The movement of amoeboid cells is mediated by actin-filled protrusions of the cell surface, pseudopodia [1]. Correlated means that a cell is more likely to move in a direction similar to its previous direction of movement. This tendency to move in the same direction is called persistence, and the duration of the correlation is the persistence time. Cells with strong persistence make few turns, move for prolonged periods of time in the same direction, and thereby penetrate the environment. This suggests that persistence may have a major impact on how cells colonize a new environment, such as during food seeking, morphogenesis and metastasis. Cells moving without persistence need a chemotaxis bias for each new pseudopod, while cells moving persistently will accumulate directional accuracy at each subsequent pseudopod

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