Ultrasound imaging is used around the world to help visualize developing babies and diagnose diseases. Sound waves bounce off the tissues, revealing their different densities and shapes. The next step in ultrasound technology is to image not just anatomy, but specific cells and molecules deeper in the body, such as those associated with tumors or bacteria in our gut.

A new study from Caltech outlines how protein engineering techniques might help achieve this milestone. The researchers engineered protein-shelled nanostructures called gas vesicles--which reflect sound waves--to exhibit new properties useful for ultrasound technologies. In the future, these gas vesicles could be administered to a patient to visualize tissues of interest. The modified gas vesicles were shown to: give off more distinct signals, making them easier to image; target specific cell types; and help create color ultrasound images.

"It's somewhat like engineering with molecular Legos," says assistant professor of chemical engineering and Heritage Principal Investigator Mikhail Shapiro, who is the senior author of a new paper about the research published in this month's issue of the journal ACS Nano and featured on the journal's cover.

"We can swap different protein 'pieces' on the surface of gas vesicles to alter their targeting properties and to visualize multiple molecules in different colors."

"Today, ultrasound is mostly anatomical," says Anupama Lakshmanan, a graduate student in Shapiro's lab and lead author of the study. "We want to bring it down to the molecular and cellular level."

In 2014, Shapiro first discovered the potential use of gas vesicles in ultrasound imaging. These gas-filled structures are naturally occurring in water-dwelling single-celled organisms, such as Anabaena flos-aquae, a species of cyanobacteria that forms filamentous clumps of multicell chains. The gas vesicles help the organisms control how much they float and thus their exposure to sunlight at the water's surface. Shapiro realized that the vesicles would readily reflect sound waves during ultrasound imaging, and ultimately demonstrated this using mice.

In the latest research, Shapiro and his team set out to give the gas vesicles new properties by engineering gas vesicle protein C, or GvpC, a protein naturally found on the surface of vesicles that gives them mechanical strength and prevents them from collapsing. The protein can be engineered to have different sizes, with longer versions of the protein producing stronger and stiffer nanostructures.

Ultrasound Homepage