Biosensor May Lead to New Drugs, Sensory Organs on a Chip – ScienceDaily

A synthetic biosensor that mimics the properties found in cell membranes and provides an electronic readout of activity could lead to a better understanding of cell biology, development of new drugs, and the creation of on-chip sensory organs capable of detecting chemicals, similar to the nose’s method. And tongues work.

A study, “Cell-Free Synthesis Becomes Electrical: A Dual Optical and Electronic Biosensor Competes with Direct Channel Integration in a Membrane Supported Electrode,” was published January 18 in Synthetic Biology Journal of the American Chemical Society.

The bioengineering feat described in the paper uses synthetic biology to reconfigure the cell membrane and its embedded proteins, which are the gatekeepers of cellular functions. The conductive sensing platform allows an electronic readout of protein activation. Being able to test whether and how a molecule interacts with proteins in the cell membrane could generate a large number of applications.

But embedding transmembrane proteins into sensors was known to be difficult until the study authors combined bioelectronic sensors with a novel protein synthesis approach.

“This technology really allows us to study these proteins in ways that would be very difficult, if not impossible, with current technology,” said first author Zachary Manzer, PhD student in the lab of senior author Susan Daniel, Fred H. Rhodes. Professor and Director of the Robert Frederick Smith School of Chemical and Biomolecular Engineering at Cornell Engineering.

Proteins within cell membranes perform many important functions, including communicating with the environment, catalyzing chemical reactions, and moving compounds and ions across membranes. When a transmembrane protein receptor is activated, charged ions move across a transmembrane channel, triggering a function in the cell. For example, neurons in the brain or muscle cells fire when signals from nerves open channels for charged calcium ions.

The researchers created a biosensor that starts with a conductive polymer, which is soft and easy to work with, atop a stent that works together as a computer-monitored electrical circuit. A layer of lipid molecules, which make up the membrane, sits on top of the polymer, and proteins of interest are enclosed within the lipid.

In this proof-of-concept, the researchers created a cell-free platform that allowed them to mount a model protein directly into this artificial membrane. The system has built-in dual read technology. Because the sensor components are transparent, researchers can use optical techniques, such as engineering proteins that fluoresce when activated, that allow scientists to study the fundamentals through a microscope, observing what happens to the protein itself during the cellular process. They can also record electronic activity to see how the protein works by designing smart circuits.

“This is the first demonstration of the exploitation of cell-free synthesis of membrane proteins in biosensors,” said Daniel. “There is no reason why we should not be able to express different types of proteins in this general platform.”

Currently, researchers have used proteins grown and extracted from living cells for similar applications, but given this advance, users will not have to grow the proteins in cells and then harvest them and incorporate them into the membrane platform. Instead, they can synthesize it directly from DNA, the basic template for proteins.

“We can bypass the entire process of the cell as a protein-producing factory, and manufacture the proteins ourselves,” Daniel said.

With such a system, a drug chemist interested in a particular protein involved in a disease might stream potential therapeutic molecules through that protein to see how it responds. Or a scientist looking to create an environmental sensor could put on the platform a specific protein that is sensitive to a chemical or pollutant, such as those found in lake water.

“If you think about your nose or your tongue, every time you smell or taste something, the ion channels fire,” Manzer said. Scientists can now take the proteins that get activated when we smell something and translate the results into this electronic system for sensing things that might not be detectable with a chemical sensor.

The new sensor opens the door for pharmacologists to research how to make non-opioid pain medications, or drugs to treat Alzheimer’s or Parkinson’s disease, that interact with cell membrane proteins.

Surajit Ghosh, a postdoctoral researcher in Daniel’s lab, is a co-first author. Neha Kamat, assistant professor of biomedical engineering at Northwestern University, is a co-senior author on the research.

The study was funded by the National Science Foundation, the Air Force Office of Scientific Research, the American Heart Association, the National Institute of General Medical Sciences, and the Defense Advanced Research Projects Agency.

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