Polarization-Sensitive Two-Photon Microscopy for a Label-Free Amyloid Structural Characterization

Our goal is to develop new optical markers and techniques for the detection of protein aggregates called amyloids. They are involved in a range of diseases such as Alzheimer’s disease and type two diabetes. So in order to cure these diseases, we need to have techniques to visualize amyloids.

We demonstrated that two-photon microscopy can be used to detect amyloid fibril orientation inside amyloid superstructures. It can be achieved not only using amyloid-specific dyes, but also by utilizing the autofluorescence of amyloids. Since our technique operates on nonlinear optical phenomena, it can achieve reduced angular photoselection, enhance axial resolution, lower light scattering, lower phototoxicity, and deeper sample penetration when compared to the one-photon fluorescence microscopic technique.

Polarization-sensitive two-photon fluorescence microscopy is a promising tool to image internal structure of various complex biological structures, not only protein aggregates, but also DNA vesicles and lipid membranes.