A new study published in Nature Communications could help biologists understand how various types of migratory cells, such as immune cells, find their way through tissues in the human body.
The research, by scientists at McGill University in Montreal and the Radboud University Medical Center in the Netherlands, focuses on a complex of proteins, known as podosomes, found in the membrane of migratory cells and in certain invasive cancer cells. In essence, podosomes mechanically push on the cell membrane, enabling the cell to probe its surroundings and select its migration path through the tissue matrix.
Previous studies of cells in tissue culture have shown that individual podosomes occur in a network or cluster where their components assemble and disassemble rapidly in migrating cells. Visually, the networks look like city hubs (podosomes) connected by road-like spokes, composed of actin cytoskeleton filaments. Biologists have been trying to understand the complex dynamics and function of these networks in migratory cells.
(About this video) A living dendritic cell moves across a microscope slide for seven hours. The cellular protein actin is linked to a luminescent protein. This causes glowing dots on the cell surface. These are the podosomes which help the cell to scan the terrain. Clusters of podosomes work here as a unit together. This video is from a publication in Nature Communications: nature.com/articles/ncomms13127. (Radboud University Medical Center)
“The findings mark an important step in unraveling the complexities of cell mechano-sensing and migration -- both in normal cell function, as in immune cells, and potentially for pathological invasion in various types of cancer cells that have similar structures,” says Prof. Paul Wiseman of McGill.
The new study combines fluorescence microscopy imaging of human immune dendritic cells, done in Prof. Alesssandra Cambi’s laboratory in the Netherlands, with image analysis using new biophysical methods developed in Wiseman’s lab at McGill. These techniques revealed that podosome assembly and disassembly are coordinated within the networks, with connections and mechanical communication among neighboring podosomes that helps orchestrate the interplay between a cell’s migration and sensing of its tissue matrix.
Financial support for the research was provided by the EU NANO-VISTA project, the Human Frontiers Science Program, and the Natural Sciences and Engineering Research Council of Canada.
“Actomyosin-dependent dynamic spatial pattern of cytoskeletal components drive mesoscale podosome organization,” Marjolein B.M. Meddens et al, Nature Communications, 10 October 2016. doi:10.1038/ncomms13127