The proteins, found on and embedded in the surface – or lipid bilayer – of human cells are largely responsible for allowing or blocking a substances’ transport into the cell; a crucial function in the delivery of a therapy.
However previous analysis methods, such as tagging with fluorescent markers or extracting, do not always accurately reflect how the proteins work because they only “pinpoint” the binding event, leaving out any other reactions in the process.
Now using an analysis technique, known as surface plasmon resonance (SPR) microscopy, researchers say they can improve the understanding of cell-pathogen interactions by providing a full run down of surface proteins’ native functions and structures.
“It allows us to determine the kinetic constants of membrane proteins in their native membrane environment, and to map the distribution of membrane proteins in the cell membrane and the local association and dissociation rate constants of membrane proteins to different ligands,” the researchers, led by Nongjian Tao, said.
Tao, director of the Center for Bioelectronics and Biosensors at Arizona State University, said the discover could open doors for drug delivery, adding: “Membrane proteins are the most popular drug targets accounting for more than half of all the present drug targets, including both large antibody based and small-molecule drugs.”
How it works
SPR has already been applied in the study of binding kinetics when looking at extracted proteins. However Tao says the process has so far been unsuccessful because extracted proteins often lose the characteristics they would have when embedded in a cell membrane’s lipid matrix.
“For this reason, a tool allowing for both spatial and temporal study of membrane protein distribution in real time is highly desirable,” a spokesperson for the Arizona State said.
In the study, published in Nature Chemistry, the team adapt the technique so that it can be used in situ using a thin, reflective film of gold.
When the polarized light hits the surface of the gold plasmon waves are generated creating waves “much like in water”.
The plasmon waves are then disrupted when any nanoscale activity – including membrane protein interaction – occurs, causing a measurable change in light reflectivity, which the new microscopy method converts into an image.
“We anticipate that the SPRM approach will have a broad impact on the study of the biological activities of membrane proteins in their native states, and on the discovery of drugs that target membrane proteins, including both monoclonal antibody drugs and small-molecule drugs, by competitive assay,” Tao said.