Journal Article

Nanoscale characterization of the biomolecular corona by cryo-electron microscopy, cryo-electron tomography, and image simulation

Basu, Kaustuv, Ashkarran, Aliakbar, Vali, Hojatollah, Mahmoudi, Morteza, Sheibani, Sara, Ejtehadi, Mohammad Reza, Bui, Khanh Huy, Ichikawa, Muneyoshi, Presley, John F., Farnudi, Ali

2021

Overview

The biological identity of nanoparticles (NPs) is established by their interactions with a wide range of biomolecules around their surfaces after exposure to biological media. Understanding the true nature of the biomolecular corona (BC) in its native state is, therefore, essential for its safe and efficient application in clinical settings. The fundamental challenge is to visualize the biomolecules within the corona and their relationship/association to the surface of the NPs. Using a synergistic application of cryo-electron microscopy, cryo-electron tomography, and three-dimensional reconstruction, we revealed the unique morphological details of the biomolecules and their distribution/association with the surface of polystyrene NPs at a nanoscale resolution. The analysis of the BC at a single NP level and its variability among NPs in the same sample, and the discovery of the presence of nonspecific biomolecules in plasma residues, enable more precise characterization of NPs, improving predictions of their safety and efficacies. Understanding the biomolecular corona is of key importance to nanomedicine. Here, the authors report on cryo-electron and tomographic imaging of the corona formed on model nanoparticles and the 3D reconstruction of the corona to study the distribution and association of the biomolecules with the nanoparticle.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 147/143 / 147/28 / 631/61/350/354 / 639/925/350 / 639/925/352 / Biochemistry, Molecular Biology / Biomolecules / Computer Simulation / Cryoelectron Microscopy - methods / Electron Microscope Tomography - methods / Electron microscopy / Humanities and Social Sciences / Humans / Image reconstruction / Imaging, Three-Dimensional - methods / Life Sciences / Microscopy / Microscopy, Electron, Transmission - methods / multidisciplinary / Nanoparticles / Nanoparticles - chemistry / Nanoparticles - ultrastructure / Nanotechnology / Plasma - chemistry / Polystyrene / Polystyrene resins / Polystyrenes - chemistry / Protein Corona - chemistry / Reproducibility of Results / Science / Science (multidisciplinary) / Three dimensional models / Tomography / Transmission electron microscopy