From Model Membranes to Human Interfaces: Lipid Self-assembly, Gradients and Environmental Responses

Biological membranes and human interfaces are maintained under non-equilibrium conditions, where they are constantly exposed to different stimuli. The aim of this work is to advance our knowledge of human interfaces and evaluate how they respond to stimuli they naturally encounter, such as fluctuations in external humidity conditions, temperature, or UVB irradiation. In the first part of this thesis work, the behavior of model systems inspired by human interfaces such as lung surfactant and tear film lipid layer (TFLL) is investigated. Mixtures of phospholipids or phospholipids:triolein dispersed in water are added to a drying-cell setup, where the solutions naturally form multilayer films at the capillary edge exposed to ambient air. The structural characterization along the water gradient is performed by means of synchrotron X-ray mapping, while the composition gradient is traced either by Confocal Raman Microscopy or Confocal fluorescence Microscopy using fluorescent probes. Taken together, the results show that the lipids segregate along the hydration gradient in the vicinity of the air interface. For the DOPC:DPPC systems, the composition gradient preferentially forms a solid gel lamellar phase characterized by shorter-range interbilayer repulsion and reduced swelling in drier conditions. This finding shows that the solutes partition according to their ability to swell in water, which can be generalized to a broad range of soft-matter systems under non-equilibrium hydration gradients. For a system composed of polar and non-polar lipids (DOPC:DOPE:triolein) in water, a pronounced phase segregation in the vicinity of the air interface is observed. The isotropic oil-rich phase wets the lamellar multilayer from both sides and preferentially accumulates at the dry interface over time. These findings highlight a mechanistic framework for how lipid layers covering drying interfaces, such as the TFLL, can maintain the balance between lubrication and barrier integrity. In the second part of this thesis work, the responses of different components of the outermost skin layer, stratum corneum (SC), are evaluated with respect to external stimuli such as temperature and levels of hydration. The behavior of SC lipids in a water gradient is evaluated by employing the drying-cell setup in combination with the same experimental techniques. The results show that the SC lipids respond to the changes in hydration in a functional way, by altering the balance between solid and fluid lipids within a solid lamellar structure. Furthermore, the antioxidative and structural responses of the SC components to UVB radiation and oxidative stress are evaluated. The results show that UVB has a strong effect on the antioxidative properties of native catalase, while the structural and molecular characteristics of the SC matrix that surrounds the enzyme are largely unchanged for comparably high UVB doses. Taken together, these results highlight the structural integrity of the SC layer and introduce a new experimental approach to evaluate the response of the SC components, which can in turn prove useful knowledge to improve transdermal delivery processes.