Magneto-acoustic protein nanostructures for non-invasive imaging of tissue mechanics in vivo

Abstract

Measuring cellular and tissue mechanics inside intact living organisms is essential for interrogating the roles of force in physiological and disease processes, and is a major goal in the field of mechanobiology. However, existing biosensors for 3D tissue mechanics, primarily based on fluorescent emissions and deformable materials, are limited for in vivo measurement due to the limited light penetration and poor material stability inside intact, living organisms. While magneto-motive ultrasound (MMUS), which uses superparamagnetic nanoparticles as imaging contrast agents, has emerged as a promising modality for real-time in vivo imaging of tissue mechanics, it has poor sensitivity and spatiotemporal resolution. To overcome these limitations, we introduce magneto-gas vesicles (MGVs), a unique class of protein nanostructures based on gas vesicles and magnetic nanoparticles that produces differential ultrasound signals in response to varying mechanical properties of surrounding tissues. These hybrid protein nanostructures significantly improve signal strength and detection sensitivity. Furthermore, MGVs enable non-invasive, long-term, and quantitative measurement of mechanical properties within 3D tissues and organs in vivo. We demonstrated the performance of MGV-based mechano-sensors in vitro, in fibrosis models of organoids, and in vivo in mouse liver fibrosis models.

Magneto-Mechanical Approach in Biomedicine: Benefits, Challenges, and Future Perspectives

“…However, some necessary technical developments are still needed [ 103 , 108 ]. Nevertheless, the MMUS technique has some limitations, such as a poor signal-to-noise ratio, a comparatively low spatiotemporal resolution, and can be improved by using magneto-gas vesicles (MGVs) as alternative contrast agents [ 109 ]. Gas vesicles (GVs) represents air-filled protein nanostructures, which can be easily isolated from photosynthetic microorganisms [ 110 ].…”