Sensing Dynamically Evolved Short-Range Nanomechanical Forces in Fast-Mutating Single Viral Spike Proteins

Understanding changes in the mechanical features of a single protein from a mutated virus while establishing its relation to the point mutations is critical in developing new inhibitory routes to tackle the uncontrollable spread of the virus. Addressing this, herein, the chemomechanical features of a single spike protein are quantified from alpha, beta, and gamma variants of SARS-CoV-2. Integrated amplitude-modulation atomic force microscopy is used with dynamic force-distance curve (FDC) spectroscopy, in combination with theoretical models, to quantify Young's modulus, stiffness, adhesion forces, van der Waals forces, and the dissipative energy of single spike proteins. These obtained nanomechanical properties can be correlated with mutations in the individual proteins. Therefore, this work opens new possibilities to understand how the mechanical properties of a single spike protein relate to the viral functions. Additionally, single-protein nanomechanical experiments enable a variety of applications that, collectively, may build up a new portfolio of understanding protein biochemistry during the evolution of viruses.

Automated summary

Understanding the mechanical changes in a mutated virus's single protein and its relation to point mutations is crucial for developing new inhibitory routes to control the virus's uncontrollable spread. In this study, the chemomechanical features of a single spike protein in the alpha, beta, and gamma variants of SARS-CoV-2 were quantified using integrated amplitude-modulation atomic force microscopy and dynamic force-distance curve spectroscopy. These nanomechanical properties can be correlated with individual protein mutations, providing new insights into the relationship between the mechanical properties of a single spike protein and viral functions. Furthermore, single-protein nanomechanical experiments have the potential to enhance our understanding of protein biochemistry during virus evolution.