In a recent poster presentation, Rory Staunton of Arizona State University and his colleagues compare the physiology of normal and cancerous cells, observing intriguing distinctions that may be used to improve diagnosis and treatment of deadly disease.
The poster was presented on April 5th, for the Physical Sciences-Oncology Center’s Network Investigators Meeting, held in National Harbor, Maryland. Staunton’s effort was subsequently rewarded by judges at the conference and selected as one of three outstanding poster presentations from the 70 entrants displayed at the meeting.
Staunton, a first year graduate student studying experimental nanobiophysics in professor Robert Ros’ lab at the Center for Biological Physics, explores the mechanical properties of cells. He explains that such properties offer valuable clues to cellular physiology, behavior and critically, the potential for the cells to metastasize. By examining cells with a physicist’s eye, researchers like Staunton hope to better understand the behavior and trajectory of these cells in ways not possible through a purely biology-based approach.
The work is part of an ambitious, multi-institute consortium devoted to a fresh approach to cancer study, using materials and techniques common to the physical sciences. The Physical Sciences-Oncology Center (PSOC) initiative involves Arizona State University, in conjunction with 11 other institutions, receiving $22.7 million in initial funding from the National Institutes of Health’s National Cancer Institute.
To investigate the mechanical properties of cancer cells, Staunton measures these cells using a combined atomic force microscope and confocal laser scanning microscope (AFM/CLSM), with fluorescence lifetime imaging (FLIM). The AFM is used to indent the cells in order to determine the Young’s modulus, a quantitative measure of a material’s stiffness. The CLSM is used to optically image the cells in order to see how stiffness varies in regions near different subcellular structures like the nucleus. FLIM is a technique that exploits differences that arise in the decay rates of fluorescent dyes in differing conditions (such as pH or ion concentration) to learn more about the local environment inside the cells. Future experiments will take advantage of fluorescence for detailed study of specific proteins involved in cell mechanics.
Results of Staunton’s research confirm earlier findings indicating that the nuclei of cancer cells are softer in texture than normal cells and display greater elasticity. Staunton stresses the importance of examining cells in an environment that better approximates their normal conditions in the body than in traditional microscopy studies. Rather than existing as isolated entities, cells are enmeshed in a network of fibers and proteins known as the extracellular matrix or ECM. “Not only do cells push and pull against the ECM and their neighbors within it, but they use it as a ‘telephone’ to send signals to other cells and as a ‘refrigerator’ to store nutrients for later,” Staunton said.
The subtle relationships between cells and the ECM they inhabit were examined in the current study by means of specialized techniques known as force spectroscopy and time-resolved fluorescence microscopy. Distinctions were observed in the response to indentation of the cancerous cells, compared with their normal counterparts. Staunton’s poster shows raw AFM data of force-distance plots. A tell-tale “scimitar” shape observed in cancer cells is not seen in normal cells, a point meriting further investigation. Staunton hopes continued research will explore these findings in greater detail. “Everyone working in this field that we’ve talked to about our project has been enthusiastic about the potential of our techniques to shine light on some unanswered questions in cancer biology. Moving from 2D to 3D environments is definitely the way to go.”
Written by Richard Harth
Biodesign Institute Science Writer