Cross-β Amyloid Nanohybrids Loaded With Cytochrome C Exhibit Superactivity in Organic Solvents^†

The present study reports the development of a unique class of Cytochrome C (CytC)-loaded cross-beta amyloid nanohybrids. The peroxidase activity of the bound CytC increased up to two orders of magnitude in organic solvents compared to the activity of unbound CytC in water. The amyloid sequences used in the study feature the nucleating core ¹⁷LVFF²¹ of the beta amyloid (Aβ), which assembled to form homogenous fibers and nanotubes. The morphology and exposed surface of the amyloid nanohydrids critically modulated the CytC activity. A CytC–Ac-KLVFFAE-NH₂ hybrid featuring nanofiber morphology showed 308-fold higher activity than unbound CytC in water, which increased to 450-fold with the nanotube morphology of CytC–Ac-KLVFFAL-NH₂. Notably, activity declined substantially when the exposed surface charge was detuned by replacing lysine with histidine, thus underpinning the importance of surface charge. This enzyme–amyloid nanohybrid system could facilitate the technological application of enzymes.