Accessing Intracellular Protein Crystals for Electron Diffraction Using Fluorescence-Guided  Cryo-FIB Lamella Preparation

Solving protein structures from intracellular crystals remains challenging, particularly for proteins with low crystallization efficiency or that are difficult to purify. It requires reliable localization and precise targeting of rare crystals within the vitrified cellular environment, followed by controlled preparation of thin lamellae for cryo-TEM analysis. This workflow relies on accurate correlation between cryo-light microscopy and cryo-FIB. 

Discover how fluorescence-guided cryo-FIB milling addresses these challenges by enabling reproducible localization of intracellular protein crystals in their native environment, without the need for purification, and their site-specific thinning into lamellae suitable for high-resolution TEM imaging and electron diffraction.