Abstract

Cell adhesion and migration are essential for the evolution, organization, and repair of living organisms. An example of a combination of these processes is the formation of new blood vessels (angiogenesis), which is mediated by a directed migration and adhesion of endothelial cells (ECs). Angiogenesis is an essential part of wound healing and a prerequisite of cancerous tumor growth. We investigated the effect of the amphiphilic compound arachidonic acid (AA) on EC adhesion and migration by combining live cell imaging with biophysical analysis methods. AA significantly influenced both EC adhesion and migration, in either a stimulating or inhibiting fashion depending on AA concentration. The temporal evolution of cell adhesion area was well described by a two-phase model. In the first phase, the spreading dynamics were independent of AA concentration. In the latter phase, the spreading dynamics increased at low AA concentrations and decreased at high AA concentrations. AA also affected EC migration; though the instantaneous speed of individual cells remained independent of AA concentration, the individual cells lost their sense of direction upon addition of AA, thus giving rise to an overall decrease in the collective motion of a confluent EC monolayer into vacant space. Addition of AA also caused ECs to become more elongated, this possibly being related to incorporation of AA in the EC membrane thus mediating a change in the viscosity of the membrane. Hence, AA is a promising non-receptor specific regulator of wound healing and angiogenesis.

Highlights

  • For many physiological processes, it is of the utmost importance that the cells move in a directed fashion biasing their motility in response to the environment

  • This implies that the first stages of the adhesion processes cannot be visualized through differential interference contrast (DIC) microscopy; they can be visualized by confocal reflection microscopy

  • The cells spread out rapidly; their dynamics were independent of arachidonic acid (AA) concentration and comparable to the passive spreading of a fluid droplet contained in a viscous shell

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Summary

Introduction

It is of the utmost importance that the cells move in a directed fashion biasing their motility in response to the environment. Angiogenesis is an essential part of wound healing and a prerequisite for metastasis [1,2], it is seen in relation to pathologies such as rheumatoid arthritis, age-related macular degeneration, and pathological diabetic blindness [2,3]. For these reasons, there has been a considerable interest in the adhesion and biased migration of cells, e.g., how these processes depend on interaction, or lack of interaction, between the cell and its environment [4,5]. During the collective EC migration, considerable traction forces are exerted [7]; they arise predominantly many cell rows behind the leading front edge, so though the leader cells play an important role in cell guidance, the physical forces they exert are only a small part of that exerted by the entire migration EC monolayer [8]

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