Ultrastrong adhesion to human skin: Calcium as a key regulator of noncovalent interactions.

Calcium is a critical regulator of skin adhesion, stabilizing one of the strongest noncovalent biomolecular interactions ever recorded. Using in vitro and in silico single-molecule force spectroscopy, we demonstrate that calcium ions (Ca) are essential for the ultrastrong binding between the serine-aspartate repeat protein D (SdrD) adhesin and the human skin protein desmoglein-1 (DSG-1), withstanding forces exceeding 2 nanonewtons. Ca ions stabilize both the SdrD complex and the mechanically robust SdrD B-domains, which exhibit unprecedented folding strength. In the context of atopic dermatitis (AD), disrupted calcium gradients amplify SdrD interactions, which could potentially intensify virulence. Furthermore, abnormal DSG-1 distribution on AD-affected skin enhances bacterial adhesion. These findings provide crucial insights into the calcium-dependent regulation of bacterial adhesion and folding, suggesting possible therapeutic targets to combat infections.