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Life Sciences 6.6

Cell shape reveals protein patterns drug companies need to understand

Researchers mapped over 1 million cells to show how protein production shifts based on cell shape—a hidden layer of biology that drug developers and diagnostics firms have largely ignored. The finding could help companies predict drug side effects and design therapies that target specific cellular states, not just disease pathways.

Originaltitel: Cell shapes decode molecular phenotypes in image-based spatial proteomics

Abstrakt

<p>Cellular and tissue structures arise from a few cell shapes, which undergo transformations based on biophysical constraints. Despite links between signaling pathways and cellular geometry, whole-proteome orchestration in association with cell shape is underexplored. In this study, over 1 million single cells stained for 11,998 proteins across 11 cell lines in the Human Protein Atlas were analyzed for organelle, pathway, and single-protein levels in association with cellular shapespace. We found that cell and nuclear shapes across cell lines exist in a shared continuum. The subcellular organelle topology varies across cell lines but remains consistent within each cell line's shapespace. At the single-protein level, cells of different shapes in the same cell-cycle phase might be preparing for different fates, and many non-cell-cycle proteins expressed shape-based abundance variation. Using a shape-based coordinate framework, we analyzed the distribution shift of protein spatial localization under drug perturbation.</p>

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