Biomolecular piezoelectric materials are envisioned for advanced biomedical applications for their robust piezoelectricity, biocompatibility, and flexibility. Here, we report the piezoelectric property of amyloid fibrils derived from three distinct proteins: lysozyme, insulin, and amyloid-β. We found that piezoelectric properties are dependent on the extent of the β-sheet structure and the extent of fibril anisotropy. We have observed the piezoelectric constant value in the range of 24-42 pm/V for fibrils made of lysozyme/insulin/amyloid-β, and for the sheet/bundle-like structure of lysozyme aggregates, the value becomes 62 pm/V. These piezoelectric constant values are 4-10 times higher than the native lysozyme/insulin/amyloid proteins. Computational studies show that extension of the β-sheet structure produces an asymmetric arrangement of charges (in creating dipole moment) and mechanical stress induces an aligned orientation of these dipoles that results in a piezoelectric effect. It is shown that these piezoelectric fibrils can harvest mechanical as well as ultrasound-based energy to produce a voltage of up to 1 V and a current of up to 13 nA. These fibrils are employed for reactive oxygen species (ROS) generation under ultrasound exposure and utilized for ultrasonic degradation of organic pollutants or killing of cancer cells via intracellular ROS generation under ultrasound exposure. Our findings demonstrate that the piezoelectric property of protein fibrils has potential for wireless therapeutic applications and may have physiological roles that are yet to be explored.
Keywords: amyloid fibril; cancer therapy; energy harvesting; insulin; lysozyme; piezoelectricity; reactive oxygen species.