Resonant second-harmonic-generation circular-dichroism microscopy reveals molecular chirality in native biological tissues

TL;DR

This paper introduces a nonlinear microscopy technique that enhances the detection of molecular chirality in biological tissues, overcoming limitations of traditional linear methods by providing high-contrast, high-resolution spectral imaging.

Contribution

The study demonstrates that second-harmonic-generation circular dichroism microscopy can effectively reveal molecular chirality in native tissues with improved contrast and spatial resolution.

Findings

Resonant spectral responses observed in collagen tissues.

Chirality-driven responses confirmed through protein denaturation.

Method surpasses linear optical activity limitations.

Abstract

Conventional linear optical activity effects are widely used for studying chiral materials. However, poor contrast and artifacts due to sample anisotropy limit the applicability of these methods. Here we demonstrate that nonlinear second-harmonic-generation circular dichroism spectral microscopy can overcome these limits. In intact collagenous tissues, clear spectral resonance is observed with sub-micrometer spatial resolution. By performing gradual protein denaturation studies, we show that the resonant responses are dominantly due to the molecular chirality.