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Cell signalling

Can fixation fake phase separation?

Irgen-Gioro S, Yoshida S, Walling V, et al. · eLife · 2022

Open access · cc by · source: Europe PMC

Comparing the same U2OS cells live vs after PFA showed FET-family IDR puncta increase—and can appear where none existed—warning that fixed-cell LLPS can be artefactual.

Study at a glance

Design
Animal / in-vitro — Live vs 4% PFA-fixed imaging of FET-family IDR condensates in U2OS cells
N
N=3 · Three FET-family IDRs (FUS, EWS, TAF15) compared live vs fixed
Population
U2OS cells transiently expressing EGFP-IDR-NLS constructs
Outcome
Fixation-induced changes in apparent LLPS puncta metrics

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Key findings

After fixation, puncta increased in number, size, and contrast; homogeneous EWS-IDR nuclei could gain many discrete puncta; all three quantified metrics rose significantly.

Methodology

Imaged EGFP-tagged FUS/EWS/TAF15 IDRs before and after typical 4% PFA fixation and quantified puncta number, roughness, and punctate percentage.

Limitations

Does not mean all fixed condensates are false, but shows fixation alone can change LLPS appearance.

How this study connects

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