New ‘nanoneedles’ puncture cell membrane to release payload on command.
Synthetic biology uses natural molecules and assembles them into a system that acts unnaturally. The ability to control the transfer of molecules through cellular membranes is an important function in synthetic biology. However, building self-contained modules with designer properties, and then integrating them into host cells without adverse effects, is an enormous challenge. Now, a study from researchers at Harvard University introduces a novel mechanical method for controlling release of molecules inside cells at a nanoscale level. The team state they have developed retractable nanoneedles using ‘R bodies’, that can extend to puncture cellular membranes and release molecules on command. The study is published in the journal American Chemical Society Synthetic Biology.
Previous studies show that R bodies respond to pH levels to extend from a tightly bound coil to a long, thin structure akin to a nanoscale needle or javelin. In nature, the bacteria containing R bodies are shed by a killer strain of single-celled organisms called paramecia. When a paramecium of a different strain ingests these shed bacteria containing R bodies, a difference in pH level between the two strains causes the R bodies to extend and puncture the bacteria’s cell walls, releasing toxins that kill the host paramecium. The current study shows that R bodies are biological machines that can be used to break through cell membranes which don’t consume molecular fuel and are extremely robust.
The current study shows that R bodies present a physical rather than genetic strategy for manipulating cells. Results show that at high pH levels, R bodies resemble a coil of ribbon and at lower pH levels, they undergo a conformational change converting them into pointy hollow tubes capable of puncturing through membranes, breaking that barrier and releasing any cargo contained inside. Data findings show that by modifying the pH level that triggers this response, R bodies become a tunable platform for controlling release of toxins or therapies.
The lab state that what’s also unique about R bodies is their reversibility and although they extend in low pH, they retract back into a tight coil when the pH level rises. They go on to add that since bacterial and eukaryotic cells all contain compartmentalized membranes, a reversible system for breaking barriers establishes a mechanical strategy for precisely controlling cells. The findings show that R bodies are capable of acting as synthetic pH-dependent pistons that can puncture E. coli membranes to release the trapped content.
The team surmise that R bodies now represent a whole new way of controlling delivery of beneficial molecules such as biologic therapies, pharmaceutical drugs or other payloads to specific cells. They go on to add that this is a great example of how the global medical community can mine living systems for unique biological elements and adapt them to develop programmable technologies for high value applications using synthetic biology. For the future, the researchers state this advance could potentially lead to a range of applications in biotechnology and medicine such as creation of new programmable biomaterials, drug delivery, and ecosystem management.