Associate Professor at UC Irvine, Co-founder of Embryologic
Image Credit: UCI News
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Presentation Title: Biophysical Characterization of Cancer Metabolism: Multiparametric Imaging and Phenotypic Tracking in Mitochondrial Dynamics
Authors: Michelle A. Digman, Giulia Tedeschi, Lorenzo Scipioni, Austin E. Lefebvre, Francesco Palomba.
Department of Biomedical Engineering and the Laboratory for Fluorescence Dynamics, University of California Irvine, Irvine, CA, USA.
Abstract: The reorganization and distribution of mitochondria have been extensively examined within neuronal cells, evidencing their critical role in meeting localized bioenergetic needs and facilitating the removal of impaired or malfunctioning mitochondria1,2. The influence of mitochondrial spatial dynamics within cancer cells, however, remains largely uncharted territory. To investigate these complex and nuanced interactions and their impact on cellular functions, we developed and applied advanced imaging techniques to monitor mitochondrial movement, assess their functionality, and understand their contribution to the overall metabolic state of the cell. We have created a user input-independent mitochondria tracker capable of analyzing mitochondrial dynamics at sub-pixel resolutions. Our software, called “Mitometer” (available at GitHub)3, is capable of tracking individual mitochondria in timelapse fluorescence images, and can furthermore detect fission and fusion dynamics between adjacent mitochondria4. Moreover, our research involves the multiplexing of various imaging techniques, including the phasor approach to fluorescence lifetime Imaging microscopy (FLIM) measurements of NADH, spectral phasors, and second harmonic generation (SHG) with Phasor analysis of Local Image Correlation Spectroscopy (PLICS). These advanced imaging approaches offer a comprehensive understanding of mitochondrial behavior and metabolic signatures, providing insights into how cancer cells exploit unique mitochondrial populations to facilitate their metastatic dissemination. By further evaluating the spheroids-extracellular matrix interaction using SHG with PLICS, our research aims to characterize the cellular microenvironment and collagen remodeling in breast cancer spheroids. These comprehensive methods not only enhance our understanding of cancer cell behavior but also hold the potential to identify novel therapeutic targets for disrupting the metastatic process. Overall, our work aims to unravel the intricate relationship between mitochondrial dynamics and cancer progression, potentially paving the way for targeted therapeutic interventions to impede metastatic spread.
References:
1 Baloh, R. H. Mitochondrial Dynamics and Peripheral Neuropathy. The Neuroscientist, 14(1):12-18, 2008.
2 Westermann, B.. Mitochondrial fusion and fission in cell life and death. Nature Reviews Molecular Cell Biology, 11(12):872-884, 2010.
3 https://github.com/aelefebv/Mitometer
4 Lefebvre AEYT, Ma D, Kessenbrock K, Lawson DA, Digman MA. Automated segmentation and tracking of mitochondria in live-cell time-lapse images. Nat Methods. 2021; 18(9): 1091-1102.
