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.
"The proteins are like the framing rods of an airplane fuselage. You use them to determine the mechanics of the structure." Shapiro says.
In one experiment, the scientists removed the strengthening protein from gas vesicles and then administered the engineered vesicles to mice and performed ultrasound imaging. Compared to normal vesicles, the modified vesicles vibrated more in response to sound waves, and thus resonated with harmonic frequencies. Harmonics are created when sound waves bounce around, for instance in a violin, and form new waves with doubled and tripled frequencies. Harmonics are not readily created in natural tissues, making the vesicles stand out in ultrasound images.
In another set of experiments, the researchers demonstrated how the gas vesicles could be made to target certain tissues in the body. They genetically engineered the vesicles to display various cellular targets, such as an amino acid sequence that recognizes proteins called integrins that are overproduced in tumor cells.
"Adding these functionalities to the gas vesicles is like snapping on a new Lego piece; it's a modular system," says Shapiro.
The team also showed how multicolor ultrasound images might be created. Conventional ultrasound images appear black and white. Shapiro's group created an approach for imaging three different types of gas vesicles as separate "colors" based on their differential ability to resist collapse under pressure. The vesicles themselves do not appear in different colors, but they can be assigned colors based on their different properties.
To demonstrate this, the team made three different versions of the vesicles with varying strengths of the GvpC protein. They then increased the ultrasound pressures, causing the variant populations to successively collapse one by one. As each population collapsed, the overall ultrasound signal decreased in proportion to the amount of that variant in the sample, and this signal change was then mapped to a specific color. In the future, if each variant population targeted a specific cell type, researchers would be able to visualize the cells in multiple colors.
"You might be able to see tumor cells versus the immune cells attacking the tumor, and thus monitor the progress of a medical treatment," says Shapiro.
The ACS Nano paper, entitled "Molecular Engineering Of Acoustic Protein Nanostructures," was funded by the National Institutes of Health, the Defense Advanced Research Projects Agency, the Heritage Research Institute for the Advancement of Medicine and Science at Caltech, and the Burroughs Wellcome Fund. Other Caltech authors include graduate student Arash Farhadi, undergraduate Suchita Nety, research assistant Audrey Lee-Gosselin, and postdoctoral scholars Raymond Bourdeau and David Maresca.
Whitney Clavin | EurekAlert!
Atomic-level motion may drive bacteria's ability to evade immune system defenses
24.04.2017 | Indiana University
Two-dimensional melting of hard spheres experimentally unravelled after 60 years
24.04.2017 | University of Oxford
More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.
Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...
Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.
"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...
The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.
Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...
The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...
Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.
Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...
20.04.2017 | Event News
18.04.2017 | Event News
03.04.2017 | Event News
24.04.2017 | Physics and Astronomy
24.04.2017 | Materials Sciences
24.04.2017 | Life Sciences