Cryo-Electron Microscopy

Cryo-electron microscopy (cryo-EM) is a structural biology technique in which biological molecules are flash-frozen in vitreous ice and imaged with an electron beam, producing two-dimensional projections that are computationally reconstructed into three-dimensional density maps via single-particle reconstruction. It does not require crystallization, which means it can capture large macromolecular complexes, membrane proteins, and conformationally heterogeneous samples that X-ray crystallography cannot access.\n\nThe 2017 Nobel Prize in Chemistry recognized cryo-EM's transformation of structural biology from a discipline constrained by crystallization to one limited only by detector technology and computational power. But the method has its own epistemic price: because reconstruction requires classifying particles into discrete conformational states, cryo-EM subtly enforces a categorical ontology on what may be continuous conformational ensembles.\n\nCryo-EM did not eliminate the filter. It replaced the crystallization filter with the classification filter — and the classification filter, being invisible, is harder to question.\n\n\n