Wednesday, 14 December 2011

The Fastest Cells in the World

On your marks, get set…and polymerise your actin microfilaments.

The results of the first ever World Cell Race are in and crawling into first place was a fetal bone marrow stem cell with a blistering top speed of 5.2 microns per minute. Fifty labs from around the world fielded athletes, who competed over a distance of 400 microns on glass slides coated with strips of a grippy substance called fibronectin—the cell equivalent of a running track.

Behind the fun, however, is a serious research topic: investigating how cells move with the aim of better understanding cancer metastasis and embryo development.

Moving is not a particularly simple task when you're a single cell. It's through an awe-inspiring demonstration of self-organisation that the numerous signalling pathways and molecular building blocks work together to generate movement. But a complete understanding of the complex interactions involved remains a huge challenge in cell biology. 

The Koch Institute Galleries: A Fibroblast Reaches Out, Version #2

The first step involves the cell reaching out a foot-like structure (image above) and is followed by retraction of the tail. The cell's scaffolding network, shown in red and green, is integral to this process. Long filaments of a protein called actin run the length of the cell and provide the mechanical force to push the membrane outwards. These filaments are anchored to the substrate on which the cells move (in the cell race, this was the fibronectin). New actin building blocks are added to the front of these filaments at the same rate as the rear ends fall apart. As the actin filaments grow in a treadmill-like process, adhesions between the filaments and the substrate are constantly formed at the front of the cell and released at the rear, causing the cell body to roll forwards around the actin network.

The 'clutch' shown in the image acts to couple the actin filaments to the subtrate on which the cell is crawling. Addition of actin monomers to the front of the filament pushes the membrane forwards while dissociation of the filament at the rear of the cell allows the tail to retract. Image source

One of the unanswered questions, however, is what causes the retraction of the rear of the cells. A paper recently published in Proceedings of the National Academy of Science sought to investigate this using a type of fish epithelial cell called a keratocyte (which incidentally placed highly in the World Cell Race). These cells can detach fragments lacking many organelles including a nucleus while still maintaining the ability to move, providing scientists with a simple model for looking at motility.

The key finding was that the cell’s membrane basically acts as an inflexible bag, stretched taut by the actin network. The leading edge of the cell is pushed forwards by the actin filaments while, at the rear, the network is weakened by the disassembly process and is crushed by the membrane tension, leading to retraction. In this way, membrane tension couples protrusion at the front with retraction at the rear.

And the paper includes some pretty videos too (link):

A better understanding of how cells move has a particular importance to developing new anti-cancer drugs. The transition of cancer cells to metastasis, where they spread to other parts of the body, is dependant on remodelling of the actin network. Therefore, drugs which interfere with the actin cytoskeleton have a huge potential for the future treatment of advanced forms of cancer.

No comments:

Post a Comment