Acute high shear stress enhances fungal cell/substrate adhesion.

Mechanical forces shape biological functions at all levels of life: biomolecules, cells, tissues, and organs. Shear flow, i.e., the transfer of momentum from regions of high momentum to those of lower momentum, influences the formation of microbial biofilms. Biofilms are complex structures composed of living cells and extracellular matrix that protects microbes from the host immune system, antimicrobial drugs, and physical damage. Despite the diversity of microbial morphology, behavior, and life cycle, biofilm formation is a conserved, multi-step process that follows a common sequence across microbial species. The initial step of this process is the adhesion of a microbe to a surface. This step is controlled by interfacial properties, including surface architecture, hydrophobicity, and composition, as well as environmental factors such as pH, nutrient availability, and physical/mechanical forces. Cell-surface adhesion molecules play a central role in the initiation of biofilm formation. In cellular fungi such as Saccharomyces cerevisiae and Candida albicans, adhesins such as Flo11p and ALS1p mediate attachment to host tissues and abiotic surfaces. The expression of these adhesins is tightly regulated by environmental conditions allowing fungi to rapidly adapt and colonize new niches. Once expressed, external shear forces modulate their activity, changing their conformation and organization in the cell wall and enhancing their adhesive properties. Previous work has demonstrated that shear forces below 2 Pa are needed for this mechanical enhancement to adhesion and that the force-dependent remodeling of the cell wall is a slow process. In this article, we demonstrate that exposure to acute high hydrodynamic shear stresses enhances and activates the adhesion of the two yeast species, S. cerevisiae and C. albicans. Using microfluidics and a new flocculation-based adhesion assay-termed as the bead adhesion precipitation assay-we show that a short exposure to a high threshold level of shear strain significantly enhances the adhesive capacity of yeasts.IMPORTANCEMechanical forces play integral roles in the fungal life cycle, impacting their metabolism, morphology, and biofilm organization. Sheer force has been demonstrated to control fungal cell adhesion by activating cell wall adhesion proteins, altering the tertiary structure of adhesion proteins, and reorganizing the display of these activated molecules on the surface of the cell. However, there is a limit. High levels of sheer force have been demonstrated to overcome cell-surface adhesion, resulting in a reduction of the number of cells on a surface. In this article, we show that cells exposed to high levels of shear rapidly respond to these forces and adapt by becoming more adhesive to surfaces. These results demonstrate that fungal cells adapt quickly to high shear and that this information needs to be considered when controlling biofilm formation and in the design of biomedical devices.