Engineering acoustic biomolecules as dynamic molecular sensors for ultrasound

Abstract

Ultrasound is currently limited in its ability to image dynamic molecular and cellular processes due to the lack of appropriate contrast agents. Gas Vesicles (GVs) - hollow protein nanostructures isolated from buoyant microbes, have emerged as a new class of nanoscale imaging agents for ultrasound (Shapiro et al., Nat. Nano. 2014). The genetic encodability of these acoustic biomolecules provides a unique platform for engineering mechanical and functional properties at the protein level. Recently, we demonstrated that removal or sequence modification of a key GV shell protein results in nanostructures with enhanced non-linear contrast as well as tunable collapse pressures for multiplexed imaging (Lakshmanan et al., ACS Nano 2016; Maresca et al., Appl. Phys. Lett. 2017). Now, we extend this platform to engineer GVs whose ultrasound signals change dynamically in response to the activity of specific molecules in their environment. In particular, we set out to produce GVs that change their non-linear ultrasound contrast in response to specific proteases, an important class of enzymes underlying homeostatic and disease processes and a target of drug discovery.

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