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Laser Phase Plate Cryo-Electron Microscopy

12 hours ago
  • #cellular imaging
  • #cryo-electron microscopy
  • #structural biology
  • A new technology called a laser phase plate uses a laser 100 million times brighter than the Sun to significantly enhance image contrast in cryo-electron microscopy (cryo-EM), enabling the visualization of faint proteins inside intact cells.
  • This advancement addresses a long-standing contrast problem in cryo-EM, potentially allowing scientists to image over 50% of functional proteins in their native cellular environments, up from less than 1% previously.
  • Two variants have been developed: a single-laser phase plate and a dual-laser crossed laser phase plate (xLPP), the latter designed to reduce artifacts and improve reliability for broader adoption.
  • Proof-of-principle experiments on purified proteins like aldolase and hemoglobin showed resolution improvements of up to 44%, with the xLPP achieving near-theoretical resolution limits on apoferritin.
  • The technology is expected to revolutionize cryo-electron tomography (cryo-ET) by providing high-contrast, atomic-detail views of proteins interacting within cells, advancing understanding of diseases linked to cellular processes.
  • Biohub's collaboration with UC Berkeley accelerated development over seven years, compressing decades of progress, and includes open data sharing via the CryoET Data Portal to benefit the global research community.
  • The laser phase plate is integral to Biohub's Virtual Biology Initiative, a $500-million effort to generate cellular datasets for AI training, aiming to map molecular interactions in health and disease at atomic resolution.