Abstract

Cell migration on microlanes represents a suitable and simple platform for the exploration of the molecular mechanisms underlying cell cytoskeleton dynamics. Here, we report on the quasi-periodic movement of cells confined in stripe-shaped microlanes. We observe persistent polarized cell shapes and directed pole-to-pole motion within the microlanes. Cells depolarize at one end of a given microlane, followed by delayed repolarization towards the opposite end. We analyze cell motility via the spatial velocity distribution, the velocity frequency spectrum and the reversal time as a measure for depolarization and spontaneous repolarization of cells at the microlane ends. The frequent encounters of a boundary in the stripe geometry provides a robust framework for quantitative investigations of the cytoskeleton protrusion and repolarization dynamics. In a first advance to rigorously test physical models of cell migration, we find that the statistics of the cell migration is recapitulated by a Cellular Potts model with a minimal description of cytoskeleton dynamics. Using LifeAct-GFP transfected cells and microlanes with differently shaped ends, we show that the local deformation of the leading cell edge in response to the tip geometry can locally either amplify or quench actin polymerization, while leaving the average reversal times unaffected.

Highlights

  • Cells navigate in complex environments and undergo morphological changes via dynamic reorganization of the actin cytoskeleton [1, 2]

  • We investigate single cells that migrate within short microlanes

  • In this form of confinement, cells exhibit a pole-to-pole migration mode. This behavior is quantified by the dominant oscillation frequency, the spatial distribution of cell positions and the persistent velocity of polarized migrating cells as a function of microlane length

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Summary

Introduction

Cells navigate in complex environments and undergo morphological changes via dynamic reorganization of the actin cytoskeleton [1, 2]. Movement is generated by cyclic phases of protrusion, adhesion to the extracellular environment, and actomyosin-driven retraction of the cell rear. Actin polymerization and crosslinking prevails in the advancement of filaments, protrusions and lamellipodia. Unraveling the mechanisms underlying actin transport, polymerization dynamics, and their regulation by Rho family GTPases are central challenges towards an intricate understanding of cell migration. The dynamics of actin show many peculiarities, including traveling wave patterns [3,4,5,6], retrograde actin flow at the leading edge [2, 7,8,9], protrusion-retraction cycles as well as persistent polarity [5, 10]. In 2D cell culture, the actomyosin-driven shape changes of the cell body lead to phenotypic migratory modes that

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