Abstract

BackgroundMany cells communicate through the production of diffusible signaling molecules that accumulate and once a critical concentration has been reached, can activate or repress a number of target genes in a process termed quorum sensing (QS). In the social amoeba Dictyostelium discoideum, QS plays an important role during development. However little is known about its effect on cell migration especially in the growth phase.Methods and FindingsTo investigate the role of cell density on cell migration in the growth phase, we use multisite timelapse microscopy and automated cell tracking. This analysis reveals a high heterogeneity within a given cell population, and the necessity to use large data sets to draw reliable conclusions on cell motion. In average, motion is persistent for short periods of time (), but normal diffusive behavior is recovered over longer time periods. The persistence times are positively correlated with the migrated distances. Interestingly, the migrated distance decreases as well with cell density. The adaptation of cell migration to cell density highlights the role of a secreted quorum sensing factor (QSF) on cell migration. Using a simple model describing the balance between the rate of QSF generation and the rate of QSF dilution, we were able to gather all experimental results into a single master curve, showing a sharp cell transition between high and low motile behaviors with increasing QSF.ConclusionThis study unambiguously demonstrates the central role played by QSF on amoeboid motion in the growth phase.

Highlights

  • Cell migration is a central process in a number of normal and pathological situations including morphogenesis, immune system response and metastasis spreading

  • This study unambiguously demonstrates the central role played by quorum sensing factor (QSF) on amoeboid motion in the growth phase

  • In order to highlight the role of QSF secreted by cells in their spontaneous migration, the evolution of cell migration was analyzed over time, in conditioned media and under controlled flow conditions

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Summary

Introduction

Cell migration is a central process in a number of normal and pathological situations including morphogenesis, immune system response and metastasis spreading. Cell movement has been classically described as a persistent random walk following the Ornstein-Uhlenbeck process [15]. This model derives from Langevin equation of motion, with white-noise. Cells follow a directed motion over a short time range, while recovering normal Brownian diffusion over longer periods. Many studies have pointed to the existence of anomalous behavior (i.e., even at long time scale, the cells do not show Brownian motion) in mammalian cells [6], and amoebas [9]. Little is known about its effect on cell migration especially in the growth phase

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