High-throughput mechanical phenotyping and transcriptomics of single cells.

Area of Science:

• Cell biology
• Biophysics
• Genomics

Background:

• Understanding cellular mechanical properties at single-cell resolution is challenging.
• Existing methods lack the ability to combine mechanophenotyping with unbiased transcriptional screening.

Purpose of the Study:

• To introduce ELASTomics, a novel method for simultaneous measurement of cell surface tension and gene expression.
• To enable joint analysis of cell mechanics and transcriptional regulation at single-cell resolution.

Main Methods:

• ELASTomics utilizes electroporation to import oligonucleotide-labelled macromolecules into cells.
• Macromolecules assess cell surface tension, and their abundance is determined by sequencing.
• The method integrates with existing single-cell sequencing technologies.

Main Results:

• ELASTomics successfully validated in diverse cancer cell lines, accurately identifying cell types and measuring surface tension.
• The study explored relationships between cell surface tension, proteins, and transcripts during hematopoietic progenitor cell differentiation.
• RRAD was identified as a regulator of cell surface tension in senescent TIG-1 cells.

Conclusions:

• ELASTomics offers a powerful tool for profiling single-cell mechanical and molecular phenotypes.
• The method facilitates dissection of the interplay between cell mechanics and gene expression in various biological contexts.
• This approach opens new avenues for research in cell biology and biophysics.