From contact angle titration to chemical force microscopy: a new route to assess the pH-dependent character of the stratum corneum

Synopsis Despite of its complex multicomponent organization and its compact architecture, the Stratum corneum (SC) is not completely impermeable to substances directly applied on the skin surface. A huge number of works have been dedicated to the understanding of the mechanisms involved in substance permeation by exploring deeper layers than the SC itself. Surprisingly, there is a poor interest in studies relating to interactions which may occur in the near‐surface region (i.e. approximately 1 nm depth) of the SC. In this work, equilibrium proton‐transfer reactions have been used as probes to define in a fundamental point of view the nature of the SC interactions with its environment. Such titration curves are investigated on ‘in vitro’ SC (isolated SC from abdominal skin tissue) and on ‘in vivo’ volar forearm (a sebum poor area). The results are discussed in term of work of adhesion and surface pKa values. Because SC can ‘reconstruct’ under heating, influence of the temperature on titration curves is investigated and the role of the different components is discussed. Different sigmoidal transitions were observed. Two common pKa values (pKa1 = 4 and pKa2 = 11.5) were clearly identified in both cases and associated to an acid–base character. By playing with the temperature of ‘in vitro’ SC, the ‘accessibility’ of polar functions was increased, thus refining the results by revealing an amphoteric character with an acid‐to‐base transition at pH 3.5 and two acid transitions at pH = 6.5 and pH = 11.5. Adhesion forces between an Atomic Force Microscopy (AFM) tip and a single isolated corneocyte through buffered liquid media were also investigated to better understand the role of the individual corneocytes. Résumé Malgré son organisation multi composante complexe et son architecture compacte, le Stratum Corneum (SC) n’est pas complètement imperméable aux substances directement appliquées à la surface de peau. Un grand nombre de travaux a été consacréà la compréhension des mécanismes impliqués dans la pénétration des substances en explorant des couches plus profondes que le SC lui‐même. Étonnamment, il y a un moindre intérêt pour les études consacrées aux interactions qui peuvent intervenir dans la région proche de la surface (c’est‐à‐dire ∼ 1nm la profondeur) du SC. Dans ce travail, les réactions de transfert d’équilibre de protons ont été utilisées comme sondes pour définir d’un point de vue fondamental la nature des interactions SC – environnement. Des courbes