FIG. 4.
Mid-infrared photothermal spectroscopy and imaging of protein aggregation. (A) Principle of mid-infrared photothermal, or optical photothermal infrared microscopy. (B) Mapping β-sheet aggregation by intensity ratio of the 1630 cm−1 over the 1650 cm−1 in primary neurons cultured with synthetic Aβ1–42. Scale bars in (f) (g) and (h) is 5 μm. Reproduced by permission from Klementieva et al., Adv. Sci. 7(6), 1903004 (2020).64 Copyright 2020 Wiley. (C) 3D visualization of intracellular tau fibrils by β-sheet structures, guided by fluorescence. Reproduced with permission from Zhao et al., Light 12(1), 147 (2023).66 Copyright 2023 Springer Nature. (D) Amyloid plaques in brain tissue labeled with Amytracker 520 with OPTIR imaging and spectra. Reproduced with permission from Prater et al., J. Med. Chem. 66(4), 2542–2549 (2023).67 Copyright 2023 American Chemical Society. (E) Structural mapping of htt aggregates (a) compared with htt103Q-GFP aggregates identified by fluorescent guidance, htt103Q aggregates identified label-free by β-sheet enrichment shifted further toward low wavenumbers; (b) htt103Q-GFP aggregate partitions into α-helix dominant core and β-sheet shell; (c) β-sheet enrichment quantified by deconvolution of amide I band of MIP spectra by small spatial distances within the aggregation complex. Reproduced with permission from Guo et al., Angew. Chem., Int. Ed. 136, e202408163 (2024).12 Copyright 2024 Wiley.