Table 2.
Effect of fixation on IF intensity and EM morphology
Fixation ProtocolIF SNR Rab5IF SNR Rab7IF SNR EEA1IF SNR APPL1EM MorphologyFigure
30-min FA 4% 2.09 ± 0.05 1.61 ± 0.03 2.00 ± 0.06 2.30 ± 0.11 – Fig. S1 A  
1-h FA 4% 1.72 ± 0.15 1.66 ± 0.07 1.76 ± 0.08 1.85 ± 0.06 +/− Fig. S1 B  
2-h FA 4% 1.62 ± 0.34 1.51 ± 0.03 1.42 ± 0.04 1.63 ± 0.03 +/− Fig. S1 C  
1-h FA 4% → ON FA 0.6% 1.44 ± 0.07 1.48 ± 0.06 1.41 ± 0.04 1.66 ± 0.06 Fig. S1 D  
ON FA 4% 1.43 ± 0.13 1.51 ± 0.02 1.24 ± 0.02 1.31 ± 0.02 Fig. S2 A  
30-min FA 4% + GA 0.2% 1.66 ± 0.06 1.36 ± 0.03 1.20 ± 0.04 1.28 ± 0.08 ++ Fig. S2 B  
2-h FA 4% + GA 0.2% 1.70 ± 0.02 1.41 ± 0.03 1.34 ± 0.05 1.39 ± 0.04 ++ Fig. S2 C  
ON FA 4% + GA 0.2% 1.64 ± 0.04 1.36 ± 0.02 1.25 ± 0.01 1.30 ± 0.02 ++ Fig. S2 D  
Fixation ProtocolIF SNR Rab5IF SNR Rab7IF SNR EEA1IF SNR APPL1EM MorphologyFigure
30-min FA 4% 2.09 ± 0.05 1.61 ± 0.03 2.00 ± 0.06 2.30 ± 0.11 – Fig. S1 A  
1-h FA 4% 1.72 ± 0.15 1.66 ± 0.07 1.76 ± 0.08 1.85 ± 0.06 +/− Fig. S1 B  
2-h FA 4% 1.62 ± 0.34 1.51 ± 0.03 1.42 ± 0.04 1.63 ± 0.03 +/− Fig. S1 C  
1-h FA 4% → ON FA 0.6% 1.44 ± 0.07 1.48 ± 0.06 1.41 ± 0.04 1.66 ± 0.06 Fig. S1 D  
ON FA 4% 1.43 ± 0.13 1.51 ± 0.02 1.24 ± 0.02 1.31 ± 0.02 Fig. S2 A  
30-min FA 4% + GA 0.2% 1.66 ± 0.06 1.36 ± 0.03 1.20 ± 0.04 1.28 ± 0.08 ++ Fig. S2 B  
2-h FA 4% + GA 0.2% 1.70 ± 0.02 1.41 ± 0.03 1.34 ± 0.05 1.39 ± 0.04 ++ Fig. S2 C  
ON FA 4% + GA 0.2% 1.64 ± 0.04 1.36 ± 0.02 1.25 ± 0.01 1.30 ± 0.02 ++ Fig. S2 D  

90-nm cryosections of HeLa cells fixed according to the indicated protocols were fluorescently labeled and imaged using fixed settings. The SNR was calculated as mean intensity value of the 0.5% brightest pixels divided by the mean intensity value of the reverse selection. Five fields-of-view were averaged for each measurement. Most SNRs significantly declined upon >30-min FA fixation or addition of GA. Morphological quality of EM images was based on blind ranking by six experienced electron microscopists. Based on these measurements, 1-h fixation with 4% FA was chosen as best fixative for CLEM.

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