Whether it’s a plant, an organ, or just a collection of cells, biological matter can only truly develop when it’s given the space to do so. Cancer cells are no exception to this, so in order for them to behave more naturally, a team of researchers used a new imaging technique that allows them to grow in true 3D space – not just along a flat glass slide.
This recent study, published in the journal Developmental Cell, showcases a new, high-resolution microscope design. Although some attempts at viewing cells or cell structures in 3D has been done before, this has only been achieved at relatively low resolutions.
This new microscope uses a powerful beam of light that brightly illuminates cells; it forces structures within them to release multiple photons at once, rather than just one as per normal fluorescence microscopy, which generates an especially luminous glow. Combined with the precision of the beam, this microscope can reveal cellular details 300 times smaller than the width of a human hair.
A skin cancer cell (red) embedded in a 3D collagen block (white and gray). Welf and Driscoll et al./Developmental Cell
Additionally, this technique views cell samples through 3D blocks of collagen, a type of protein mostly found in connective tissue within mammals. Unlike samples squashed along or between glass slides, cells can grow out into the collagen blocks, all viewable in real-time. The physical properties of the collagen block can also be altered, permitting cells to spread through it faster or slower.
To test their new device, skin and lung cancer tissue samples from a variety of afflicted patients were observed developing within the collagen blocks; immediately, the researchers noticed striking differences compared to their growth on or in traditional glass slides. Far rounder cell shapes were noticed, along with an uptick in the appearance of “blebs,” small protrusions effusing from the cells.
These blebs are thought to remove parts of the cell that are considered a threat to the cell’s overall wellbeing. Medical researchers also think that blebbing, as the process is known, actually helps these cancer cells to survive by moving their cellular material around their environment. This new imaging technique will be able to investigate this in an unprecedented manner, enlightening researchers on how skin cancer cells resist or even evade chemotherapy drugs.
A “spheroid” containing multiple lung cancer cells. Welf and Driscoll et al./Developmental Cell
The team also found that multiple cells can be placed within these collagen blocks, with their microscopic interactions all viewable in high-resolution at a variety of angles. Remarkably, the sheer volume of information this technique is already producing has required the researchers to enlist the aid of computer programs. These will observe and analyze changes in the smallest cellular components in order to reveal details that may otherwise go amiss.
“There is clear evidence that the environment strongly affects cellular behavior,” said the study’s senior author Reto Fiolka, an optical scientist at the University of Texas Southwestern Medical Center, in a statement. Only time will tell if the emergence of this new technique signals the start of the decline of the traditional microscope.
“The value of cell culture experiments on glass must at least be questioned,” he added.