Cell shapes decode molecular phenotypes in image-based spatial proteomics

Area of Science:

• Cell Biology
• Biophysics
• Proteomics

Background:

• Cellular and tissue structures originate from diverse cell shapes governed by biophysical constraints.
• The relationship between signaling pathways and cellular geometry is known, but whole-proteome orchestration concerning cell shape remains under-investigated.

Purpose of the Study:

• To explore whole-proteome orchestration in association with cell shape.
• To analyze organelle, pathway, and single-protein levels in relation to cellular shapespace.
• To investigate protein spatial localization shifts under drug perturbation using a shape-based framework.

Main Methods:

• Analysis of over 1 million single cells from 11 cell lines using the Human Protein Atlas.
• Single-cell proteomics and imaging to assess protein levels and localization.
• Development of a shape-based coordinate framework for spatial analysis.

Main Results:

• Cell and nuclear shapes across different cell lines form a shared continuum.
• Subcellular organelle topology is cell-line specific but consistent within each cell line's shapespace.
• Non-cell-cycle proteins show shape-based abundance variations, suggesting shape influences cell fate preparation.

Conclusions:

• Cell shape is a fundamental organizing principle in cellular architecture and function.
• Protein localization and abundance are significantly influenced by cellular geometry.
• A shape-based framework can reveal dynamic protein distribution changes, offering insights into drug responses.