Cyclic Mechanical Deformation of Denture PMMA Regulates Fungal Biofilm Virulence

Cyclic mechanical deformation is a well-characterized phenomenon in polymeric biomaterials under physiological mastication loading, yet its role in regulating biological responses at material interfaces remains poorly understood. Here, we investigate whether cyclic mechanical loading of denture-base poly-(methyl methacrylate) (PMMA) functions as a biomaterial-derived cue that regulates fungal biofilm behavior. This study establishes that mechanically induced Candida albicans virulence is strain dependent and extends to clinically relevant isolates, thereby improving the translational relevance of denture mechanobiology models. Biofilms of C. albicans strains with distinct filamentation capacities, including the laboratory reference strain SC5314, two clinical isolates (hyphae-defective (UR18) and hyperfilamentous (UR13)), and a hyphae-deficient (efg1ΔΔ mutant), were grown on polished and rough PMMA surfaces and subjected to physiologically relevant cyclic deformation. Results showed that cyclic loading significantly altered biofilm behavior in a Candida strain-dependent manner. Filament-competent strains exhibited increased viability, extracellular polymeric substances (EPS) production, hyphal formation, and protease secretion, with the hyperfilamentous clinical isolate showing the strongest mechanosensitive virulence response. Filament-incompetent strains still retained robust protease secretion triggered by cyclic mechanical loading, revealing that toxic enzyme production can be mechanically activated independently of hyphal growth. While surface roughness modulated response magnitude, cyclic deformation alone was sufficient to activate virulence even on polished/smooth PMMA surfaces. These findings identify cyclic mechanical deformation as a biomaterial parameter governing the biofilm behavior and virulence of clinical and laboratory fungal strains and highlight the importance of incorporating mechanical loading into the design and evaluation of polymeric biomaterials.