Biogenic gas nanostructures as ultrasonic molecular reporters
Ultrasound is among the most widely used non-invasive imaging modalities in biomedicine, 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 gas. 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.
© 2014 Macmillan Publishers Limited. Received 20 November 2012; Accepted 28 January 2014; Published online 16 March 2014. The authors thank P. Lumfor ultrasound equipment and advice, R. Zalpuri and K. McDonald for assistance with electron microscopy, K-K. Park and P. Khuri-Yakub for assistance with hydrophone measurements, E. Chérin for input on in vivo experiments and the manuscript, and A. Bar-Zion for assistance with data analysis. M.G.S. acknowledges funding from the Miller Research Institute and the Burroughs Wellcome Career Award at the Scientific Interface. Other funding was provided by California Institute for Regenerative Medicine grant RT2-02022 (D.V.S.), National Institutes of Health grant R01EB013689 (S.M.C), the Canadian Institutes of Health Research (F.S.F.) and the Terry Fox Foundation (F.S.F.). Author contributions: M.G.S. conceived and directed the study, planned the experiments, prepared the specimens, collected, analysed and interpreted the data, and wrote the manuscript, with input from all other authors. P.W.G. designed and constructed the imaging instrument and accompanying signal processing software, and assisted with initial experiments. A.N. designed, constructed and optimized the imaging instrument and accompanying signal processing software. F.S.F. and M.Y. designed, performed and analysed the data from in vivo experiments. All authors provided input on the study and experimental design, data analysis, data interpretation and the manuscript.
Accepted Version - nihms561295.pdf
Supplemental Material - nnano.2014.32-s1.pdf
Supplemental Material - nnano.2014.32-s2.mov