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A stepwise retreat: how immune cells catch pathogens

July 12, 2007

To protect us from disease our immune system employs macrophages, cells that roam our body in search of disease-causing bacteria. With the help of long tentacle-like protrusions, macrophages can catch suspicious particles, pull them towards their cell bodies, internalise and destroy them. Using a special microscopy technique, researchers from the European Molecular Biology Laboratory [EMBL] now for the first time tracked the dynamic behaviour of these tentacles in three dimensions. In the current online issue of PNAS they describe a molecular mechanism that likely underlies the tentacle movement and that could influence the design of new nanotechnologies.

The long cell protrusions that macrophages use as tentacles to go fishing for pathogens are called filopodia. The internal scaffolds of these filopodia are long, dynamic filaments consisting of rows of proteins called actin. The filaments constantly grow and shrink by adding or removing individual actin building blocks. But the dynamic properties of the filopodia and the mechanical forces that they can apply are not fully understood. Using a special microscopy technique, a team of researchers from the groups of Ernst Stelzer and Gareth Griffiths at EMBL could for the first time observe the tentacle dynamics in three dimensions and measure their properties to unprecedented detail.

"The filopodia stretch out from the cell surface and upon contact with a suspicious particle they attach to it and immediately retract to pull the particle towards the cell body," says Holger Kress, who carried out the research at EMBL and is now working at Yale University. "We expected the tentacles to move in a continuous, smooth process, but surprisingly we observed discrete steps of filopodia retraction."

Highly precise measurements allowed the scientists for the first time to determine the speed and the force of the retraction and revealed that each individual retraction step is 36 nanometres long. These parameters match the properties of a class of proteins called myosins suggesting them as the driving force of filopodia retraction. Myosins are motor proteins, proteins that move along actin filaments and transport cargo. Transporting the filopodia's internal scaffold myosins help bringing about the retraction. Likely several copies of myosin proteins act in a synchronous fashion to bring about the tentacle motion.

"The insights we gained into the properties of filopodia retraction and the possible molecular mechanism underlying them could find applications in nanotechnology," says Alexander Rohrbach, a former member of Stelzer's group, who is now a professor at the University of Freiburg. "Future synthetic nano-machines must integrate themselves into a system and have to react flexibly to changes within the system. Precisely these properties we have now observed in filopodia retraction. The fascinating principles, which we are beginning to understand, will certainly influence the design of such machines."

European Molecular Biology Laboratory