Biogenic gas nanostructures as ultrasonic molecular reporters

Abstract

Ultrasound is among the most widely used non-invasive imaging modalities in biomedicine1, but plays a surprisingly small role in molecular imaging due to a lack of suitable molecular reporters on the nanoscale. Here we introduce a new class of reporters for ultrasound based on genetically encoded gas nanostructures from microorganisms, including bacteria and archaea. Gas vesicles are gas-filled protein-shelled compartments with typical widths of 45–250 nm and lengths of 100–600 nm that exclude water and are permeable to gas2, 3. We show that gas vesicles produce stable ultrasound contrast that is readily detected in vitro and in vivo, that their genetically encoded physical properties enable multiple modes of imaging, and that contrast enhancement through aggregation permits their use as molecular biosensors.

Microscopy of Microbial Gas Vesicles

“…They include cyanobacteria, anoxygenic photosynthetic bacteria, cold-loving heterotrophic bacteria, spore-forming bacteria, and so on (Pfeifer, 2012). A (2012) and (E) from Shapiro et al (2014), with permission from the publisher.…”

“…1D). Enclosed by a 2 nm-thick hydrophobic protein shell, gas vesicles exclude water by surface tension at the hydrophobic inner surface, but permit gas from outside to freely diffuse in and out of their barrier (Shapiro et al, 2014;Walsby, 1994) (Fig. 1E).…”

“…Although gas vesicles are intensively studied in aquatic microbes such as the cyanobacterium Anabaena flos-aquae and the halophilic archaeon Halobacterium salinarum, they have been also observed even in a soil microbe and an enterobacterium (Daviso et al, 2013). As microbial gas vesicle-like structures, lipid-or protein-stabilized gas microbubbles have been used as contrast agents for conventional ultrasound imaging (Shapiro et al, 2014). However, the microbubbles are prone to collapse and bubble fragmentation.…”

“…There is a growing need in ultrasound-modulated stable contrast agents on the nanoscale or molecular reporters. Gas vesicles derived from natural biological structures could be used as nanoscale molecular reporters for ultrasound imaging, based on their hollow interiors, gas permeability, buoyancy, and optical scattering (Shapiro et al, 2014). Due to their nanoscale size, gas vesicles could potentially exit the intravascular space into solid tumors (Cherin et al, 2017).…”

NMR Hyperpolarization Techniques of Gases

“…First, they are the first genetically encodable imaging agents for ultrasound, [196] where their low density and high elasticity relative to surrounding media allows them to scatter sound waves. Secondly, their gas-filled interior, which has a different magnetic susceptibility from surrounding solution, allows GVs to produce 1 H MRI contrast in susceptibility-weighted imaging.…”