Coiled Proteins May Be Key To Targeted Cellular Drug Delivery

Bacteria-derived coiled protein ribbons – known as R bodies – could be induced to penetrate the cell membrane of select cells, thereby initiating a targeted drug delivery system. While currently-available bioengineered vesicles are capable of delivering the pharmaceutical payload to the appropriate cells, this technique lacks a reliable mechanism by which the drug is unloaded.

The R bodies are used as a defense mechanism in bacterial species that live inside single-cellular aquatic organisms, known as paramecia. Under certain conditions, the coiled R bodies are able to elongate and pierce the cell membrane of other invading bacteria, injecting toxins into the competition.

Jessica K. Polka and Pamela A. Silver, researchers from Harvard University, decided to test the effectiveness of R bodies as a drug delivery system. The researchers discovered that the R bodies could be reliably induced to unfurl once the pH of the surrounding solution was lowered.

In order to test the effectiveness of the R bodies under changing pH, the researchers expressed the R bodies inside E. coli cells. They found that 60 percent of the membranes were ruptured by the elongation of the R bodies, after the pH of the surround solution became more acidic.

“As such, these protein machines present a novel way to selectively rupture membrane compartments and will be important for programming cellular compartmentalization,” said the authors. The results of the study were published in the journal, Synthetic Biology.

According to the researchers, the elongation and retract action of the R bodies is rapid and reversible, making this biotechnology ideal for a number of targeted cellular delivery applications. In addition, these proteins could be repurposed as switches inside microelectromechanical systems (MEMS) – a new technology in the field of bioengineering.