How force drives pathogenicity: mechanoregulation of <i>Streptococcus mutans</i> adhesion to collagen

<i>Streptococcus mutans</i> is a caries-associated bacterium with the ability to adhere to the surface of oral tissues and promote biofilm formation. For this purpose, <i>S. mutans</i> expresses a range of specialized surface adhesins, among which collagen-binding proteins (CBPs) have demonstrated an important function regarding attachment to dentin, bacterial coaggregation, and extracellular matrix invasion. Understanding the mechanobiological behavior of CBPs, particularly their interaction with collagens during the process of bacterial adhesion, is crucial for developing novel strategies to prevent biofilm formation in oral and remote tissues. Therefore, this review summarizes recent evidence regarding the main mechanical properties of the relevant <i>S. mutans</i> CBPs SpaP, WapA, Cnm, and Cbm, and how their mechanobiological and adhesive characteristics play an important role in their virulence toward the host. Particularly, we will focus on how state-of-the-art interdisciplinary approaches such as atomic force microscopy (AFM)-based single-molecule force spectroscopy (SMFS) and single-cell force spectroscopy (SCFS) have been employed to characterize <i>S. mutans</i> and CBP attachment to collagen substrates and mechanical behavior in real-time and under physiological conditions. Altogether, the potential use of AFM SMFS and SCFS to explore novel anti-biofilm molecules against <i>S. mutans</i> remains an exciting possibility for the development of caries-preventive treatments in the future.