Direct Visualization and Restoration of Metallic Ion-Induced Subcellular Ultrastructural Remodeling

Analysis of cellular ultrastructure dynamics and metal ions' fate can provide insights into the interaction between living organisms and metal ions. Here, we directly visualize the distribution of biogenic metallic aggregates, ion-induced subcellular reorganization, and the corresponding regulation effect in yeast by the near-native 3D imaging approach, cryo-soft X-ray tomography (cryo-SXT). By comparative 3D morphometric assessment, we observe the gold ions disrupting cellular organelle homeostasis, resulting in noticeable distortion and folding of vacuoles, apparent fragmentation of mitochondria, extreme swelling of lipid droplets, and formation of vesicles. The reconstructed 3D architecture of treated yeast demonstrates ∼65% of Au-rich sites in the periplasm, a comprehensive quantitative assessment unobtained by TEM. We also observe some AuNPs in rarely identified subcellular sites, namely, mitochondria and vesicles. Interestingly, the amount of gold deposition is positively correlated with the volume of lipid droplets. Shifting the external starting pH to near-neutral results in the reversion of changes in organelle architectures, boosting the amount of biogenic Au nanoparticles, and increasing cell viability. This study provides a strategy to analyze the metal ions-living organism interaction from subcellular architecture and spatial localization perspectives.