Taking a look at living cancer cells in 3-D
UT Southwestern Medical Center researchers have designed and built a microscope capable of creating high-resolution, 3-D images of living cancer cells in realistic, controllable microenvironments.
“There is no microscope that allows us to look at living cells with this resolution and precision in a controlled microenvironment. We can now create 3-D images of cancer cells and record how they interact with their microenvironment via signaling,” said Dr. Gaudenz Danuser, Chair of the Lyda Hill Department of Bioinformatics and holder of the Patrick E. Haggerty Distinguished Chair in Basic Biomedical Science.
The new microscope was designed to solve a long-standing problem in biology: the need to artificially constrain cells – usually by flattening them onto glass plates in two dimensions – in order to image them clearly. The trade-off between image clarity and environmental realism has existed for centuries, researchers explained. Being able to clearly image cells in 3-D creates opportunities for researchers to make observations at a subcellular level without compromising microenvironmental control, which should open a window for addressing fundamental questions in cell biology.
“For the first time, we have image data of these processes at a resolution that allows us to computationally model, for example, the signaling patterns that may confer drug resistance in cancer cells,” explained Dr. Danuser, whose Department was formed in 2015 with an extraordinary $25 million gift from Dallas entrepreneur and philanthropist Lyda Hill. Bioinformatics provides tools for analyzing extremely large sets of research data to address scientific and clinical challenges.
The 3-D imaging approach, detailed in Developmental Cell, enables researchers to study cells in controlled microenvironments at a level of detail that should accelerate the pace of discovery in many fields of biology, Dr. Danuser explained.
“It’s a two-photon, light-sheet microscope that allows 3-D time-lapse imaging of cells deep within physiologically realistic microenvironments,” said Dr. Reto Fiolka, Assistant Professor of Cell Biology at UT Southwestern and a corresponding author of the study, which was supported by grants from the Cancer Prevention and Research Institute of Texas (CPRIT) and the National Institutes of Health.
Using the new microscope and software, the researchers created 3-D images of the detailed shapes that skin and lung cancer cells develop as they move through tissue. They also created images and movies of the dynamic activation of a key signaling molecule (PI3-kinase) that is involved in many cellular processes.