Light Scattering Detects Changes In Subcellular Structure And Organization With Connections To Cell Function

Abstract

By incorporating new models into our light scattering analysis techniques that better account for the ellipsoidal shape of cellular organelles, we can determine not only the average size, but also the average shape of an ensemble of cell nuclei in culture. This advance permitted new insight into the nucleus structure, and by providing an accurate depiction of its contribution to the light scattering signal, has also enabled an enhanced ability to analyze density correlations and therefore subcellular organization in biological cells. We will present verification of our methods and results of two new studies facilitated by these recent developments. In the first study, we used light scattering to detect statistically significant structural changes in breast cancer cells within one hour after treatment with apoptosis-inducing drugs. Two conclusions emerge: First, the ability of this technique to discern early onset of apoptosis makes it a promising tool for monitoring cancer treatments; and second, monitoring the organization of subcellular organelles could be a powerful method for studying the mechanisms of apoptosis, and perhaps other functional changes in cells. In the second study, we evaluated the deformation of stem cell nuclei as a response to engineered nanotopographical cues and the mechanical properties of their substrate. As verified by image analysis and comparison to control samples, the changes in nuclear shape due to materials' properties and nanotopography are highly significant. Additionally, these shape changes relate to modifications in stem cell adhesion and mobility, and provide a connection between environmental cues, nuclear deformation, and cellular behavior. Both studies solidified light scattering as a promising tool to assess structure in biological samples, and indicate the potential to link these structural changes to corresponding alterations in cell function.