The ability to control the transfer of molecules through cellular membranes is an important function in synthetic biology; a new study from researchers at Harvard’s Wyss Institute for Biologically Inspired Engineering and Harvard Medical School (HMS) introduces a novel mechanical method for controlling release of molecules inside cells.

Described in the American Chemical Society Synthetic Biology journal, the team describes using protein polymers known as “R bodies”, which are found in certain bacteria, as retractable nanoneedles that can extend to puncture cellular membranes and release molecules on command.

In this time-lapse, retractable protein actuators called "R bodies" -  found naturally in certain bacteria - are seen extending from barely-visible tiny coils into long pointy tubes that are capable of rupturing cell membranes. The extension is triggered by a rise in pH level. Wyss Institute researchers have harnessed these structures and are adapting them for use in mammalian cells, which could one day lead to novel mechanisms for delivering drugs and other chemicals of interest. Credit: Wyss Institute at Harvard University

"This is one of nature’s innovations, but the discovery here is our ability to translate this from nature into a system that we can now engineer and control," said Wyss Core Faculty member Pamela Silver, Ph.D., who is also Professor of Biochemistry and Systems Biology at HMS, and senior author on the study.

Functioning like a biological actuator, 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. But in synthetic biology, 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.

"Our research establishes R bodies as biological machines that we can use to break through membranes,” said Jessica Polka, Ph.D., a Postdoctoral Research Fellow at the Wyss Institute and HMS, who was first author on the study. “These actuators don’t consume molecular fuel and are extremely robust; we believe they could one day be used to deliver material to mammalian cells."

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