How migratory cells find their way through body tissue

Cambi, A.

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.

Alessandra Cambi (photo up), Marjolein Meddens and colleagues, theme Nanomedicine, together with colleagues from McGill University, Canada 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. undefined

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 discrete 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.

The new study combines fluorescence microscopy imaging of human immune dendritic cells, done in Alesssandra Cambi’s laboratory, with image analysis using new biophysical methods developed in Paul Wiseman’s lab at McGill University. These techniques revealed that podosome assembly and disassembly are mechanically 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.

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

Video how podosomes working in human dendritic cells. 

Actin (green) and mysione (purple) in a carpet of podosomes on a human dendritic cell imaged with super-resolution microscopy. In the left image can be clearly seen the actin network that connects the podosomes mutually. In the right picture you can see how almost all myosin actin strings connect to each other and pull together.

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