Framework upgrades quartz crystal microbalance analyses

A quartz crystal microbalance (QCM) measures mass changes by monitoring the frequency shifts of a quartz crystal resonator. This sensitive, label-free technique is often used for studying biomolecules such as proteins. However, the QCM signal is created through a complex interaction between biomolecule viscoelasticity and solvent hydrodynamics, making it difficult to translate these signals into physico-chemical properties.

To address this challenge, Bonet et al. presented Virtual-QCM, a theoretical and computational framework that quantitatively reproduces QCM experiments. The framework is based on first principles, incorporating hydrodynamics solvers and coarse-grained molecular models. Combining Virtual-QCM with QCM experimental data allowed the authors to precisely analyze complex viscoelastic structures.

The authors investigated intrinsically disordered proteins, which lack a fixed structure. Using Virtual-QCM and real QCM data, they were able to extract protein properties, including protein-substrate binding affinity, protein linker elongation, stiffness, and viscoelasticity, that would otherwise require demanding, expensive techniques.

Their results also showed that modifying the salt content and ion type in the solvent affected properties of the proteins, supporting the idea that disordered proteins are sensitive to their environment.

“By combining real QCM experiments with the Virtual-QCM, any scientist will be able to upgrade the QCM technique from an ultrasensitive sensor to a high-precision tool to rationalize and measure a significant list of physico-chemical properties of biomolecules and soft matter,” said author Rafael Delgado-Buscalioni.

Virtual-QCM could be applied to many organic or inorganic soft-matter systems, including proteins, viruses, bacteria, and nanoparticles. Next, the authors will test Virtual-QCM on virus-like particles and bacteria. They also plan to make Virtual-QCM available to the public with an online application.

Source: “Quantitative description of protein configuration and viscoelasticity using first-principles hydrodynamics applied to quartz crystal microbalance experiments,” by Noel F. Bonet, Pablo Palacios Alonso, Marisela Vélez, and Rafael Delgado-Buscalioni, Journal of Chemical Physics (2026). The article can be accessed at https://doi.org/10.1063/5.0323622 .