Application of Individual Particle Transmission Electron Microscopy Reconstruction in Nanoparticle Structural Analysis

doi:10.16553/j.cnki.issn1000-985x.2026.0043

Abstract

Abstract: Cryo-electron tomography （Cryo-ET） enables in situ structural elucidation of flexible biomacromolecules with structural heterogeneity under near-native conditions. However， conventional tomography suffers from issues such as large-scale image shifts and tilting errors， which often lead to reconstruction artifacts. The individual-particle electron tomography （IPET） method achieves significantly improved reconstruction accuracy and reliability by performing iterative alignment on local regions of individual particles. To address the limitation of conventional electron microscopy in accurately resolving the three-dimensional configurations of flexible and structurally heterogeneous nanomaterials， Cryo-ET combined with IPET was employed for structural characterization of nanomaterials in this study. This approach enables in situ three-dimensional characterization under near-native conditions and facilitates comprehensive acquisition of key structural information， including morphology， internal channels， and interfacial interactions. For example， the microstructure of gold nanocages clearly reveals their shell architecture and characterizes the distribution pattern of channel pathways within the shell. The three-dimensional structure of graphene-phospholipid vesicle complexes offers structural insight into the interaction between graphene and the membrane， revealing their binding sites. Structural analysis of nanofibers resolves their multilevel helical architecture and provides structural insight into their self-assembly behavior. The results demonstrate that the combination of Cryo-ET and IPET offers unique advantages for the three-dimensional structural characterization of flexible nanomaterials， and provides a new characterization approach for investigating structure-property relationships and guiding related functional design of nanomaterials. With the advantages of in situ characterization， high resolution， and adaptability to structurally heterogeneous systems， this approach shows broad potential in structural biology and nanomaterials science and may provide important technical support for elucidating disease mechanisms， new drug development， and nanomaterial design.

Key words: cryo-electron tomography; three-dimensional reconstruction; individual particle electron tomography; nanomaterial; structural analysis

CLC Number:

TB383

ZHAI Xiaobo, HUANG Xueli, ZENG Yu, YANG Liujing, XIE You. Application of Individual Particle Transmission Electron Microscopy Reconstruction in Nanoparticle Structural Analysis[J]. Journal of Synthetic Crystals, 2026, 55(8): 1313-1320.

Figures/Tables 4

Fig.1 3D construction of phospholipid vesicles by IPET. （a） Cryo-transmission electron microscopy （Cryo-TEM） images of phospholipid vesicles at different tilt angles；（b） selection of local projections of the target particle at different tilt angles；（c） 3D density map reconstructed by the local tomographic iterative algorithm （with missing-wedge correction applied）

Fig.2 Transmission images of dried gold nanocages at different tilt angles （a） and the corresponding 3D density maps at the same angles （b）；（c） slice view， with arrows indicating the channel positions. The spatial resolution is 15 ?

Fig.3 Transmission images of phospholipid membranes co-cultured with graphene at different tilt angles （a） and the corresponding 3D density maps at the same angles （b）， the arrow indicates the position of graphene. The spatial resolution is 78 ?

Fig.4 Transmission images of self-assembled nanofiber samples at different tilt angles （a） and the corresponding 3D density maps at the same angles （b）. The spatial resolution is 64 ?

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