A new angle on molecular binding: an innovative method to directly observe atomic-scale bonding
In a paper being published this week in Scientific Reports, a pair of undergraduate students working in the NYU Center for Soft Matter Research have developed a new method for observing molecular binding using Holographic Video Microscopy (HVM).
The science of molecular binding seeks to understand what physical, chemical and geometric configurations influence the tendency of two different molecules or proteins to connect—form bonds—with one another. At present, directly observing the bonding of one molecule to another in any biological system requires the attachment of fluorescent marker compounds to the target molecules. These markers provide a brighter and more distinctive signal with which researches can track the binding process. However, adding these markers may interfere with the process being measured and adds additional steps to complete an observation. Developing more accurate and efficient methods to observe this phenomenon is of particular value, as it is central to pharmaceutical and biomolecular research and technology.
Working alongside Professors David Grier and Andrew Hollingsworth as well as visiting student Francesca Soddu, recently graduated physics major and lead author Yvonne Zagzag demonstrates a new approach to observing molecular binding through the application of Holographic Video Microscopy. The group used the xSight, a commercially developed instrument which allows for the measurement of sub-nanometre changes in diameter of colloidal particles by creating and recording holograms of them. This permitted the direct observation of the chemical binding between a target molecule and a protein; biotin and avidin.
The measurement was taken by coating polystyrene microspheres with biotin and determining the diameter of the sphere before and after avidin was bonded to it. After successfully demonstrating the approach’s utility for this protocol in the paper, the team then applies it to another more complex biological system. This other system—the bonding of immunoglobulin G onto a sphere functionalized with protein A—is important for exhibiting this technique’s application to medical diagnostics.
Zagzag began the work for this project during her sophomore year in the physics major program and continued until her graduation in 2019. She has since began her PhD in physics at the University of Pennsylvania. Francesca Soddu worked alongside Zagzag as a visiting undergraduate and is now completing her graduate degree at CCNY.