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What Size Molecules Can Cryo-EM Analyze?

Published in Cryo-EM Capabilities 2 mins read

Cryo-electron microscopy (cryo-EM) is a powerful technique primarily used to determine the structure of biological macromolecules, and its capabilities regarding the size of analyzable samples have significantly advanced. When referring to "size" in the context of cryo-EM, it typically pertains to the molecular weight of the macromolecules or complexes that can be accurately reconstructed.

Currently, single-particle cryo-EM can reconstruct macromolecules with a lower particle weight limit of below 50 kilodaltons (kDa) for proteins. This capability extends even lower for nucleic acids. The field continues to progress, and it is anticipated that the eventual lower limit for analyzable particle weight could become less than approximately 20 kDa.

Understanding Molecular Weight Limits

The ability to image smaller particles is crucial for studying a wider range of biological systems, from individual protein domains to smaller signaling molecules. Reaching lower molecular weight thresholds allows researchers to:

  • Resolve smaller protein structures: Many important proteins and protein domains fall into the lower molecular weight range.
  • Investigate nucleic acid structures: Cryo-EM's capability for nucleic acids is already lower than for proteins, opening doors for detailed studies of RNA and DNA.
  • Understand fundamental biological processes: Many basic cellular functions are governed by the interactions of relatively small macromolecules.

Cryo-EM Molecular Weight Capabilities

The following table summarizes the typical molecular weight ranges for samples analyzable by single-particle cryo-EM:

Sample Type Current Lower Limit Potential Future Lower Limit
Proteins Below 50 kDa Less than ~20 kDa
Nucleic Acids Even lower than for proteins Potentially very low

This continuous improvement in the ability to reconstruct smaller and smaller molecules highlights cryo-EM's growing importance in structural biology, enabling the visualization of biological machinery at an unprecedented scale and detail. To learn more about specific advancements in the field, further details can be explored in publications regarding cryo-EM applications.