University of Massachusetts Medical School Faculty Publications
UMMS Affiliation
RNA Therapeutics Institute
Publication Date
2021-02-19
Document Type
Article Preprint
Disciplines
Biophysics
Abstract
Image simulation plays a central role in the development and practice of high-resolution electron microscopy, including transmission electron microscopy of frozen-hydrated specimens (cryo-EM). Simulating images with contrast that matches the contrast observed in experimental images remains challenging, especially for amorphous samples. Current state-of-the-art simulators apply post hoc scaling to approximate empirical solvent contrast, attenuated image intensity due to specimen thickness, and amplitude contrast. This practice fails for images that require spatially variable scaling, e.g., simulations of a crowded or cellular environment. Modeling both the signal and the noise accurately is necessary to simulate images of biological specimens with contrast that is correct on an absolute scale. To do so, we introduce the “Frozen-Plasmon” method which explicitly models spatially variable inelastic scattering processes in cryo-EM specimens. This approach produces amplitude contrast that depends on the atomic composition of the specimen, reproduces the total inelastic mean free path as observed experimentally and allows for the incorporation of radiation damage in the simulation. Taken in combination with a new mathematical formulation for accurately sampling the tabulated atomic scattering potentials onto a Cartesian grid, we also demonstrate how the matched-filter concept can be used to quantitatively compare model and experiment. The simulator is available as a standalone program, implemented in C++ with multi-threaded parallelism using the computational imaging system for Transmission Electron Microscopy (cisTEM.)
Keywords
biophysics, Cryo-TEM simulations, image simulation
Rights and Permissions
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC 4.0 International license.
DOI of Published Version
10.1101/2021.02.19.431636
Source
bioRxiv 2021.02.19.431636; doi: https://doi.org/10.1101/2021.02.19.431636. Link to preprint on bioRxiv.
Journal/Book/Conference Title
bioRxiv
Repository Citation
Himes BA, Grigorieff N. (2021). Cryo-TEM simulations of amorphous radiation-sensitive samples using multislice wave propagation [preprint]. University of Massachusetts Medical School Faculty Publications. https://doi.org/10.1101/2021.02.19.431636. Retrieved from https://escholarship.umassmed.edu/faculty_pubs/1932
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial 4.0 License
Comments
This article is a preprint. Preprints are preliminary reports of work that have not been certified by peer review.