Secrets of plague unlocked with stunning new imaging techniques

Researchers at Sandia National Laboratories have developed a super-resolution microscopy technique that would answer long-held questions about exactly how and why a cell's defenses fail against some invaders, such as plague, while successfully fending off others like E.coli. The approach has revealed never-before-seen details of the cell membrane, which could open doors to new diagnostic, prevention and treatment techniques.

 
The difference between what was previously seen on the cell surface (left image) is dramatically different from what Jeri Timlin, Jesse Aaron, and Bryan Carson are now able to image (right). Orange areas correspond to the bacterial lipopolysaccharide (LPS), derived from E. coli, and the green areas correspond to the cell's TLR4 receptors. (Photo by Jeri Timlin, Jesse Aaron and Bryan Carson)

''We're trying to do molecular biology with a microscope, but in order to do that, we must be able to look at things on a molecular scale,'' says Jesse Aaron, postdoctoral appointee at Sandia Labs.

The cell membrane is a bustling hub of activity on a miniscule scale. While providing structure and housing the cell's interior, the membrane regulates movement of materials in and out of the cell, controls adhesion to other objects and coordinates the cell's communications and subsequent actions through signaling.

Receptor proteins on the surface of immune cells, known as toll-like receptors (TLRs), are tasked with recognising intruders, or antigens. The TLR4 member of this receptor family responds to certain types of bacteria by detecting lipopolysaccharides (LPS) present on their surface. TLR4 proteins then alert the cell and activate an immune response.

Using imaging techniques they developed, Sandia researchers Aaron, Jeri Timlin and Bryan Carson discovered that TLR4 proteins cluster in the membrane when confronted with LPS derived from E.coli, which increases cell signaling and response.

Interestingly, LPS derived from the bacteria that cause plague, Yersinia pestis, do not cause the same effects. This could explain why some pathogens are able to thwart the human immune system.