An efficient trucking system might involve a small number of vesicles specialized to carry just FcRn, so Björkman expected to see a few vesicles containing a lot of FcRn and antibody. Instead, cells had a lot of vesicles holding only a little of the cargo. Moreover, the vesicles weren't neat spheres. They were “looped and bent, and twisted around each other. They almost tied themselves in knots,” says Björkman. “It was a tangled mess I wasn't expecting.” Previous results from two-dimensional imaging had suggested a more orderly grouping of small vesicles, where vesicles typically travel across cells on protein tracks. But in Björkman's observations few vesicles were lined up with these tracks. She suspects that once the longer tubes expunge the smaller vesicles, those small vesicles move randomly through the cell until they collide with the membrane.

The delivery step also bore a surprise. As expected, vesicles arrived at the blood vessel side of the cell and fused with the membrane to release their antibody load. But the vesicles also carried the tell-tale hexagons and pentagons of clathrin, a molecule that helps form vesicles by constructing a cage around them. Conventional wisdom holds that vesicles have to shed this cage before they deliver their cargo, so Björkman was surprised to see clathrin there. The observation might reveal a new mechanism for releasing cargo, says Björkman. For instance, vesicles might shed only a small part of their clathrin coating to quickly jettison antibodies and immediately return to pick up a new load.

Björkman is now after a more detailed view of antibody transport, employing other methods to witness transport in action. “In EM, everything is in a vacuum; nothing is alive,” says Björkman. “But in fluorescent live imaging we can take 5 frames per second and watch vesicles move.” Gazing at the mysteries those movies hold could provide action-packed evidence for some of Björkman's speculations.

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