Electron tomography's three-dimensional images give surprising insights into cell trafficking.

By tagging antibodies with gold particles, Pamela Björkman's group has visualized, using electron tomography, how a newborn rat absorbs these antibodies from its mother's milk and transports them within a cell. The resulting images reveal several surprises about key transport vesicles (blue) among other cellular components (various colors).

Lava lamps seem simple at first, but stare at one for a while and the complexity behind how the colored blobs stretch, tangle, and pinch off becomes evident. Cells use similarly complex and dynamic structures for transport, according to HHMI investigator Pamela Björkman of the California Institute of Technology. New images from her lab reveal ornate structures cells use to shuttle proteins that help a newborn fend off infections.

Developing fetuses and newborns don't have fully formed immune systems. Instead, the mother provides protection by donating her antibodies. A newborn absorbs them from its mother's milk with the help of a protein called FcRn. The protein sits in the outer membrane of intestine cells and grabs antibodies as they pass through the gut. A sac called a vesicle pinches off from the membrane, carries FcRn and antibodies to the other side of the cell, and dispenses antibodies into the baby's bloodstream.

		Vesicles in Motion See more images generated through electron tomography. Images: Wanzhong He / Björkman lab.

Björkman has devoted years to studying high-resolution details of the protein's shape by shining x-rays through FcRn crystals. Because making crystals out of membrane proteins is tricky, she has been able to study only the portion of the protein that pokes out from the membrane—the part that clamps down on antibodies. She knew, however, that the protein behaved differently when it sat in a membrane. Plus, the x-ray method probes the protein in isolation, and Björkman wanted to know how it worked in the intestine.

To learn more, she turned to a technique called electron tomography. The method builds on electron microscopy (EM), in which beams of electrons pass through a tissue sample to create a detailed two-dimensional image. In electron tomography, multiple images are captured while tilting the sample at different angles relative to the electron beam. The images can then be analyzed and combined into a three-dimensional picture. Björkman's team developed antibodies tagged with gold particles so that FcRn was visible when it grabbed an antibody.

Illustration: Wanzhong He / Björkman Lab

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