Real-time observation of dynamic heterogeneity of gold nanorods on plasma membrane with darkfield microscopy
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The plasma membrane possesses a complicated structure, on which the protein clusters are randomly but orderly distributed to maintain the regular morphology and function of cells. Investigating the detailed dynamic behaviors of nanoparticles (NPs) on cytomembrane is of great importance to understand cellular mechanisms and advance the bio-nano technologies for drug delivery, photothermal therapy, immunotherapy, etc. In this work, to study the dynamic heterogeneous interactions between NPs and cell membrane with high resolution, we established a simple method to efficiently track the translational and rotational diffusion of individual gold nanorods (AuNRs) on cell membranes. This method is based on that an anisotropic AuNR appears as a colored spot under a darkfield microscope (DFM) equipped with a color camera. While obtaining its lateral position, the polar angle of the AuNR can be calculated simultaneously from intensity difference between the R and G channels. Careful analysis shows that the lateral motion of single AuNRs do not follow normal Brownian diffusion, which could be attributed to their hop diffusion in the dynamically varying picket-fence structure of the live cell membrane. Furthermore, 4 different rotation-translation patterns of the AuNR are observed due to spatiotemporal heterogeneity of the cytomembrane. This simple but robust method for simultaneously obtaining the location and orientation of anisotropic plasmonic nanoparticles could be further applied to the analysis of complicated biological and biomedical processes.
Keywordssingle particle tracking gold nanorods nanoparticle cell interaction darkfield microscopy
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This work was supported by the National Natural Science Foundation of China (21127009, 21425519, 21221003, 21475071, 21605045), the Tsinghua University Startup Fund, the Taishan Scholar Program of Shandong Province (ts201511027), and the Natural Science Foundation of Shandong (2018GGX102030).
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