Browsing by Author "Berríos, Pablo"

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    How force drives pathogenicity: mechanoregulation of Streptococcus mutans adhesion to collagen
    (2025) Inostroza, Carla; Berríos, Pablo; Orellana, Ivana; Rivas-Pardo, Jaime Andrés; Aguayo Paul, Sebastián
    Streptococcus mutans is a caries-associated bacterium with the ability to adhere to the surface of oral tissues and promote biofilm formation. For this purpose, S. mutans 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 S. mutans 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 S. mutans 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 S. mutans remains an exciting possibility for the development of caries-preventive treatments in the future.
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    Royal Jelly Derived Extracellular Vesicles Modulate Microglial Nanomechanics and Inflammatory Responses
    (2025) Zavala, Gabriela; Berríos, Pablo; Sandoval, Felipe; Bravo, Graciela; Barrera, Nelson P.; Alarcón Moyano, Jéssica; Díaz Calderón, Paulo; Aguayo, Sebastián; Schuh, Christina
    BACKGROUND Microglia, the braińs resident immune cells, undergo profound mechanical and functional changes upon activation contributing to neuroinflammation, a pathological signature of many neurological diseases. Thus, new anti-inflammatory treatment options are needed that tackle these mechanobiological alterations in microglia, which remain strongly understudied. In this context, extracellular vesicles (EVs) are crucial mediators of intercellular and interkingdom communication, yet their influence on the mechanobiological properties of recipient cells remains largely unknown. Honeybee-derived Royal Jelly EVs (RJEVs) have demonstrated remarkable anti-inflammatory properties, but their impact on microglial cellular nanomechanics and uptake mechanisms remains unclear. RESULTS In this study, we used a multi-disciplinary approach to analyze the resulting biological and nanomechanical changes following the activation of human microglia and the potential effect of RJEV treatment on these mechanobiological parameters. We observed that LPS treatment was associated with decreased cellular Young’s modulus, increased membrane fluidity, and enhanced motility of microglia, indicating a more migratory and pro-inflammatory phenotype. Additionally, LPS exposure altered cellular EV uptake mechanisms by shifting preference from an equilibrium of four mechanisms to the predominance of macropinocytosis and clathrin-dependent endocytosis. Remarkably, RJEV treatment counteracted these mechanobiological changes by, in turn, increasing microglial stiffness, reducing motility, and decreasing secretion of pro-inflammatory cytokines. CONCLUSION This is the first study to demonstrate that microglial activation state dictates EV uptake mechanisms and to establish a direct link between inflammation, cellular and membrane mechanics, and EV-mediated modulation. Our findings highlight RJEVs as promising candidates for regulating neuroinflammation by targeting microglial mechanobiology as well as opening new strategies for EV-based therapeutics