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Morphology Assessment Enabled by Room-Temperature Soft-Landing in Native MS
Zihao Qi1,2, Yu-Fu Lin1, Sophie R Harvey1
1Native MS Guided Structural Biology Center, Department of Chemistry and Biochemistry, The Ohio State University, Columbus, OH, 43210, United States.
International Journal of Mass Spectrometry
|June 29, 2026
Summary
Native mass spectrometry combined with room-temperature ion soft-landing prepares protein complexes for electron microscopy. This method aids structural biology research by enabling mass analysis and shape screening of biomolecular assemblies.
Area of Science:
- Structural Biology
- Biochemistry
- Analytical Chemistry
Background:
- Native mass spectrometry (nMS) preserves non-covalent interactions in protein complexes.
- Electron microscopy requires well-prepared samples for imaging individual particles.
Purpose of the Study:
- To assess native mass spectrometry combined with room-temperature ion soft-landing for preparing protein complexes for electron microscopy.
- To evaluate and redesign ion soft-landing setups for compatibility with standard mass spectrometry workflows.
Main Methods:
- Utilized native mass spectrometry (nMS) to analyze protein complexes.
- Employed room-temperature ion soft-landing to deposit protein complexes onto surfaces.
- Performed transmission electron microscopy (TEM) for low-resolution imaging.
- Replicated and redesigned ion soft-landing instrumentation for enhanced compatibility.
Main Results:
- Successfully landed and imaged two protein complexes (TRAP and VFLIP) with low-resolution TEM, showing agreement with known structures.
- Developed a redesigned soft-landing setup that integrates with standard mass spectrometry (MS) instruments (UHMR with ExD-SID), allowing routine nMS experiments without compromising performance.
- Demonstrated the compatibility of the redesigned setup with electron capture dissociation (ExD), higher-energy collisional dissociation (HCD), and sustained off-resonance dissociation (SID) fragmentation.
Conclusions:
- Room-temperature ion soft-landing is a viable technique for preparing protein complexes for electron microscopy.
- The redesigned soft-landing setup facilitates sample preparation and evaluation in early-stage structural biology research.
- This integrated approach provides multidimensional information, including mass and shape, for biomolecular assemblies.
