Bioengineers have created a detailed guide to understand the protein interactions that lead to the formation of gas vesicles, which are naturally occurring tiny bubbles with promising applications in the medical field.
When it comes to buoyant devices, floaties aren’t particularly advanced. However, the minute air-filled bubbles that certain microorganisms utilize for buoyancy in their quest for sunlight are quite remarkable.
These tiny bubbles, known as gas vesicles (GVs), are only micrometers in size, yet they hold significant potential for various medical applications such as imaging, sensing, manipulating cells, and tracking. The challenge, however, is that scientists have yet to discover how to create effective types of GVs in a lab setting.
Researchers from Rice University have developed a guide that explains the interactions of a set of proteins that contribute to the formation of the thin shell surrounding these bubbles. By unraveling some of the intricate molecular mechanisms involved in GV formation, bioengineer George Lu and his team at the Laboratory for Synthetic Macromolecular Assemblies are advancing towards the development of new diagnostics and treatments based on these natural structures.
“GVs are basically tiny air bubbles, and they can be used with ultrasound to visualize things in our bodies such as tumors or specific organs,” explained Manuel Iburg, a postdoctoral researcher at Rice and lead author of a study published in The EMBO Journal. “Nonetheless, GVs cannot be synthesized in a lab or mass-produced, so we can’t create them from scratch.”
The GV family includes some of the smallest bubbles known and can last for months. Their ability to remain stable over long periods is largely attributed to their unique protein shell, which allows both water and gas molecules to pass through while being highly resistant to water on the inside. This quality enables GVs to retain gas even when submerged. Unlike man-made nanobubbles that require external gas, GVs extract gas from their surrounding liquid.
Water-dwelling photosynthetic bacteria that utilize GVs for buoyancy near sunlight possess specific genes that encode the proteins forming this specialized shell. However, although researchers know the appearance of these tiny bubbles and their tendency to cluster, they have not yet deciphered the protein interactions responsible for assembling these structures. Without understanding how these protein components work together, efforts to create lab-engineered GVs for healthcare must be paused.
To tackle this issue, the researchers focused on a set of 11 proteins they identified as integral to the assembly process and developed a method to observe how each protein interacts with the others within the living host cells.
“We needed to be meticulous and continually verify that our cells were still producing GVs,” Iburg remarked. “One important takeaway was that some of the GV proteins can be altered with relative ease.”
This understanding allowed the team to add or remove certain GV proteins during their tests, helping them uncover that interactions among some proteins required additional support from other proteins to properly unfold. They also monitored changes in these individual interactions throughout the GV assembly process.
“Through numerous variations and tests, we developed a comprehensive map demonstrating how these various proteins interact to produce a GV inside the cell,” Iburg noted. “Our experiments indicated that this roadmap of GV interactions is quite intricate, with numerous interconnected elements. Some GV proteins form smaller subnetworks with specific functions, some require interaction with multiple components of the assembling system, and some change their interactions over time.”
“We believe GVs have significant potential for innovative, rapid, and comfortable ultrasound-based diagnostic or therapeutic options for patients,” Lu, an assistant professor of bioengineering at Rice and a Cancer Prevention and Research Institute of Texas (CPRIT) Scholar, stated. “Our findings could also aid researchers in creating GVs that make existing therapies even more precise, convenient, and effective.”
