Organelles are highly dynamic and fulfill their function by constant motion and cooperation with each other. Current methods rely on fluorescence, leading to short observation time (via photobleaching) and experimental complexity (via multiple-labeling). While label-free microscopes promise a paradigm change in this regard, the spatiotemporal resolutions and specificity are still insufficient to study organelle interactions. Using mitochondria and lysosome as examples, the paper demonstrates that organelle-specific phase contrast microscopy (OS-PCM) can achieve automatic analysis of dynamic metrics of multiple organelles as well as their interactions from unlabeled cells for the first time. Compared to fluorescence-based methods, this method is gentle and holds great promise for label-free visualization and analysis of pan-organelle dynamics and interactions, with minimum perturbation to the cell.
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