Abstract
Lipid membranes play a crucial role in regulating the body's water balance by adjusting their properties in response to hydration. The intercellular lipid matrix of the stratum corneum (SC), the outermost skin layer, serves as the body's primary defense against environmental factors. Osmolytes, including urocanic acid (UCA) and glycerol, are key components of the natural moisturizing factor that help the SC resist osmotic stress from dry environments. This study examines the effects of UCA and glycerol (each at 5 mol %) on isolated human SC lipids. For this, different techniques were employed, offering complementary information of the system's multiscale characteristics, including humidity-scanning quartz crystal microbalance with dissipation monitoring, infrared spectroscopy, x-ray diffraction, electrical impedance spectroscopy, and studies of water loss and permeability. Our results show that UCA increases water sorption and makes lipid films more liquid-like at high relative humidity, without significantly altering the lipid lamellar structure, chain order, or orthorhombic chain packing. Lipid films containing UCA exhibited higher water loss and significantly higher model drug permeability compared to lipid films without UCA. Further, incorporation of UCA resulted in kinetically faster changes in electrical properties upon contact with aqueous solution compared with control lipids. These observations suggest that UCA reduces lipid cohesion in regions other than the acyl chain-rich leaflets, which may impact SC desquamation. In contrast, glycerol did not influence the hydration or permeability of the SC lipid matrix. However, it increased the proportion of orthorhombic domains at high humidities and slowed the kinetics of the hydration process, as evidenced by slower changes in the dielectric properties of the lipid film. These findings suggest that glycerol enhances lipid cohesion rather than increasing water uptake, which is typically the expected function of humectants. Consequently, UCA and glycerol appear to have distinct roles in maintaining epidermal homeostasis.