Intracellular dynamics are dominated by active transport driven by energetic processes far from equilibrium. Cytoskeletal restructuring, membrane motions and molecular motors use GTP and ATP to drive directed transport that is quasi-one-dimensional with speeds from 10 nm/sec to 10 microns/sec and persistence times tp as large as several seconds. Light scattering under these conditions can be in the lifetime-broadened Doppler shift regime as opposed to a random diffusive regime. The isotropic distribution of 1D transport within cells and tissues produces broad-band signatures that do not produce specific Doppler spectral peaks, but produce Doppler spectral edges that can be related to the mean squared speeds inside cells. The wDtp = 1 product provides a natural dividing line between the Doppler and the diffusive regimes, with a broad cross-over range into which many tissue-based light scattering processes fall. In this talk, I will show how the intracellular Doppler character of dynamic light scattering is derived and modeled, and provide experimental support from biodynamic imaging. Biodynamic imaging uses low-coherence digital holography to capture dynamic spectra in three dimensions from living tissue samples. Biodynamic imaging, based on changes in intracellular dynamics caused by applied therapeutics or changing environments, is expanding into multiple applications, including the selection of chemotherapy for personalized cancer care, screening of potential new therapeutics, and the selection of embryos for artificial reproductive technology. I will give an overview of these applications, describing how changes in biophysical behavior provide actionable biomarkers for clinical applications.
David D. Nolte, Zhe Li, Honggu Choi, Hao Sun, and John Turek, "3D tissue Doppler spectroscopy of intracellular dynamics: biophysics and applications (Conference Presentation)," Proc. SPIE 10504, Biophysics, Biology and Biophotonics III: the Crossroads, 105040F (Presented at SPIE BiOS: January 29, 2018; Published: 15 March 2018); https://doi.org/10.1117/12.2290517.5752159396001.
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