Consideration of sample motion in cryo-tomography based on alignment residual interpolation

Area of Science:

• Structural Biology
• Microscopy Techniques
• Computational Biology

Background:

• Beam-induced motion significantly degrades resolution in cryo-electron tomography (cryoET).
• Previous methods using polynomial models for motion correction require extensive parameter optimization, limiting practical use.
• Accurate correction of sample motion is crucial for high-resolution cryoET imaging.

Purpose of the Study:

• To develop a simplified and effective method for modeling and correcting beam-induced sample motion in cryoET.
• To improve the quality of tomograms by integrating a novel motion correction approach into the reconstruction process.
• To enhance the accessibility of advanced motion correction techniques for the cryoET community.

Main Methods:

• Utilized alignment residuals from standard fiducial-based tilt-series alignment as local motion estimates.
• Applied a smooth, closed-form scattered data interpolation technique to model the 3D sample motion.
• Integrated the derived motion model into the cryo-tomographic reconstruction workflow.

Main Results:

• Achieved tomogram quality comparable to existing polynomial-based methods.
• Demonstrated a significant simplification in determining the sample motion model.
• Overcame the major limitation of complex parameter optimization found in previous methods.

Conclusions:

• The proposed method offers an effective and simplified approach to beam-induced motion correction in cryoET.
• This technique enhances tomogram quality while being more user-friendly than prior methods.
• Expected to increase the adoption and accessibility of motion correction in cryoET.