Imaging technique captures cancer-killing cells in unprecedented 3-D detail

Researchers from Imperial College London and the University of Oxford used optical laser tweezers and a super-resolution microscope to see the inner workings of white blood cells in their highest resolution to date.

Researchers from Imperial College London (London, England) and the University of Oxford (Oxford, England) used optical laser tweezers and a super-resolution microscope to see the inner workings of white blood cells in their highest resolution to date. In the study, the researchers describe how a white blood cell rearranges its scaffolding of actin proteins on the inside of its membrane to create a hole through which it delivers deadly enzyme-filled granules to kill diseased tissue.

The study looked at a type of white blood cell called a natural killer (NK) cell. NK cells protect the body by identifying and killing diseased tissue, such as viruses and tumors. They may also play a role in the outcome of bone marrow transplants by determining whether a recipient's body rejects or accepts the donated tissue, says Prof. Daniel Davis from the Department of Life Sciences at Imperial College London, who led the research.

The scientists hope that learning more about how NK cells identify which tissues to kill and initiate the killing process could lead to better healthcare for some patients. Drugs that influence where and when NK cells kill could be included in future medical treatments, such as the targeted killing of tumors, says Prof. Davis. They may also prove useful in preventing the unwanted destruction by NK cells that may occur in transplant rejection or some auto-immune diseases.

A novel imaging technique developed in collaboration with physicists at Imperial and the use of a super-resolution microscope at the University of Oxford enabled the new visual resolution of NK cell action. To accomplish this, the researchers immobilized an NK cell and its target using a pair of optical laser tweezers so that the microscope could capture all the action at the interface between the cells. They then watched inside the NK cell as the actin filaments parted to create a tiny portal and the enzyme-filled granules moved to the portal, ready to pass out of the NK cell and onto the target to kill it.

The contact between an NK cell and its target is only about a hundredth of a millimeter across and the miniscule actin proteins and granules change position continuously over the few minutes from initial contact until the target is killed. The microscope has to be able to capture images quickly enough and in high enough visual detail in order to reveal their activity.

Using laser tweezers to manipulate the interface between live cells into a horizontal orientation means the team's microscope can take many images of the cell contact interface in rapid succession, says Prof. Paul French from the Department of Physics at Imperial College London, who helped develop the microscopy technique with colleagues in the Photonics Group. The technique has provided an unprecedented means to directly see dynamic molecular processes that go on between live cells, he says.

This study was funded by the Medical Research Council (MRC), the Biotechnology and Biological Sciences Research Council (BBSRC) and a Marie Curie Intra-European Fellowship. It also benefited from a £150,000 award from the Rector's Research Excellence Prize to reward high academic achievement in blue skies research with significant potential. Professors Daniel Davis and Paul French hold Wolfson Royal Society Research Merit Awards.

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