Label-free analysis of organelle interactions using organelle-specific phase contrast microscopy (OS-PCM)

Organelles are highly dynamic and\nfulfill their function by constant\nmotion and cooperation with each other. Current methods rely on fluorescence,\nleading to short observation time (via photobleaching) and experimental\ncomplexity (via multiple labeling). While label-free microscopes promise\na paradigm change in this regard, the spatiotemporal resolutions and\nspecificity are still insufficient to study organelle interactions.\nUsing mitochondria and lysosome as examples, we demonstrate that our\norganelle-specific phase contrast microscopy (OS-PCM) can achieve\nautomatic analysis of dynamic metrics of multiple organelles as well\nas their interactions from unlabeled cells for the first time. Compared\nto fluorescence-based methods, our method is gentle and holds great\npromise for label-free visualization and analysis of pan-organelle\ndynamics and interactions, with minimum perturbation to the cell.