Pinpointing the source of chirality in protein-nanoparticle complexes

An experiment designed to untangle spectroscopy signals coming from a complex mix of molecules and nanoparticles has revealed a surprising detail about the handedness of the self-assembled molecule-nanoparticle complexes (Science 2019: DOI: 10.1126/science.aax5415).

The advance may ultimately lead to methods for determining the chirality of individual protein molecules, a capability prized by the pharmaceutical industry. Tools for detecting molecular chirality and for distinguishing an enantiomer of a biomolecule from its mirror image are important, for example, for understanding the health effects of drugs, in which one enantiomer may be helpful and the other harmful.

Circular dichroism spectroscopy (CDS) can help by measuring the extent to which molecules rotate circularly polarized light, a property that depends on their chirality. But CDS signals tend to be weak. Researchers recently came up with a way to boost those signals by attaching metal nanoparticles to biomolecules. Shining light on complexes of proteins and gold nanorods, for example, can trigger nanorod surface plasmons—electronic oscillations that enhance the CDS signals, making them more readily detectable.

But until now, researchers have been unable to determine conclusively whether the signals detected in these protein-nanoparticle suspensions come from the chiral proteins, individual protein-covered nanorods, or aggregates of those complexes. The information may lead to strategies to design tailored probes that selectively latch onto just one molecule for detection.

A team led by Rice University’s Qingfeng Zhang, Christy F. Landes, and Stephan Link analyzed assemblies of 100-nm-long gold nanorods and bovine serum albumin (BSA), a well-studied chiral protein, and determined that the chirality signals originate exclusively from chiral nanorod-protein aggregates and from proteins wedged in the gaps between the nanorods. Individual protein-covered nanorods and symmetric aggregates—for example, ones with parallel nanorods—do not contribute to the signal. The team also found, unexpectedly, that BSA functions like a chirality-inducing glue, forming aggregates with a handedness that matches BSA’s.

University of Michigan’s Nicholas A. Kotov finds the work “intensely intellectual,” noting that studies of this type are essential for ultrasensitive detection of cancer markers and genetic mutations and other applications.