Cell Adhesion and Biofilm Development via Force-Sensitive Mechanisms: A Perspective.

Microorganisms live in environments where mechanical forces, such as fluid shear, surface tension, or pressure, shape their adhesion, biofilm formation, and maturation strategies. Microbes employ force-sensitive molecular switches embedded in surface appendages like flagella, pili, and adhesins like ALS1p or FLO11p to interpret mechanical cues. These mechanical cues trigger chemosensation or generate conformational changes in mechanosensors, thereby activating downstream signaling cascades and modulating gene expression. Ultimately, these mechanical stimuli affect microbial adhesion to surfaces, biofilm resilience, and architecture, often enhancing pathogenicity and virulence. Yet, the mechanobiological basis of these events remains underexplored. In this perspective, we discuss how bacterial and fungal systems use mechanosensation to navigate complex surfaces, underscore the challenges in monitoring real-time molecular responses to force, and explore emerging tools to reveal force-driven molecular dynamics. We highlight insights for synthetic microbiologists, materials scientists, and biomedical engineers into microbial mechanosensation and its translational potential, guiding the development of next-generation antimicrobial strategies to prevent and disrupt persistent biofilms in clinical and industrial settings.