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Six images show the inside of the human body at high resolution: cellular structures, possible new drug targets, blood vessels... They were obtained using a fundamental technique for cancer research.
Confocal microscopy is a type of advanced optical microscopy that unveils cells and their interior in great detail, and in 3D.
“Confocal microscopy is critical to understand how different cancer cells behave and how they respond to treatments,” says Isabel Peset, head of the CNIO Confocal Microscopy Unit.
To be able to see structures within cells at high resolution, scientists first need to stain these structures. Different staining techniques allow different biomarkers – and hence different processes- to be seen simultaneously.
Some techniques make it possible to visualize living cells. Super-resolution methods that are capable to resolve 50-nanometer structures such as mitochondria have also been developed (one nanometer is one millionth of a millimeter).
“Thanks to super-resolution techniques, structures that at first seemed diffuse have been shown to be very well defined instead. Now we can understand much better how the cell works,” adds Peset.
All about cells
Mitochondria (green) provide energy to cells and therefore to our body. Microtubules (red) are the skeleton of cells and are involved in cell division, cell motility and cell transport. Cell nuclei (blue) contain all the genetic material. The cell membrane (white) is the boundary between the inside and outside of cells. Actin (cyan) is also part of the skeleton and lysosomes (yellow) are the cell digestive system. Treatments and diseases can affect these essential structures. Visualising them simultaneously allow us to understand what can be affected.
The origin of everything
The cell nucleus (blue) contains the genetic material, the DNA making the genes. Genes carry the commands governing the functioning of the cell. The image shows the nucleoli (red and green), which are multifunctional compartments in the nuclei. Their number and size vary according to cell types and diseases. Visualization of the nuclei opens up the possibility to find new biomarkers and treatments.
Where our energy comes from
This super-resolution microscopy image shows two essential cellular structures: mitochondria (green) and microtubules (red). Mitochondria provide energy to cells and therefore to our whole body. Microtubules form the equivalent of the skeleton of cells; they are involved in cell division and intracellular trafficking, among other functions.
Defensive cells lay siege to the tumor
White blood cells CD4 lymphocytes, in red, and CD8 lymphocytes, in yellow, infiltrate between the cells of the epithelium lining the tonsils (green). The spatial distribution of immune cells and their relationship to the tumor, as well as to other immune cells, can be studied only with advanced light microscopy.
How tumors feed
The formation of blood vessels is key in the development of cancer, as it allows the arrival of nutrients and oxygen to tumor cells. Studying the factors involved in the generation of these vessels is essential to find new treatments to prevent tumor survival. This confocal microscopy image shows how the morphology of blood vessels (green and red) in tumor areas is different from non-tumor areas.
The protective shield of telomeres
Recent studies show that the elimination of a protein related to telomeres (the ends of chromosomes), called TRF1, prevents the origin and progression of lung cancer and glioblastoma (a type of brain tumor). Confocal microscopy makes it possible to visualize telomeres in the cell nucleus, measure their size and study the proteins protecting them. This is essential to understant the role of telomeres in cancer. This confocal microscopy image shows Trf1 blood vessels (green) (red) and nuclei (blue) in mouse glioblastoma.