Interfasedynamica van fosfolipiden en longsurfactant

In the first part of this work, a complete analysis of the effect of temperature and surface pressure on the interfacial shear rheology of the main lung surfactant phospholipid DPPC is performed. The monolayer is shown to behave as a viscoelastic liquid with a domain structure. At low frequencies and for a thermally structured monolayer, the interaction of the molecules within the domains can be probed. The low frequency limit of the complex viscosity is measured over a wide range of temperatures and surface pressures. The effects of temperature and surface pressure on the low frequency viscosity can be analysed in terms of the effects of free molecular area. At higher frequencies or following a preshear at high shear rates, the elastic modulus becomes more important. Most probably an elasticity due to defects at the edge of the domains in the layer is probed. Preshearing refines the structure and induces more defects. As a result, disagreeing interfacial rheology results in various publications might be due to different pretreatments of the interface. Finally, the obtained dataset and scaling laws enable us to described the surface viscosity, and its dependence at physiological conditions of DPPC. Secondly, the effect of interfacial rheology on the mobility of thin surfactant films is investigated. Three lung surfactant replacements used in clinical practice (Survanta, Curosurf and Infasurf) are compared. Additionally, also the effect of the protein human serum albumin (HSA) is investigated. To fully mimic the condition in the lung not only the temperature in the setup is controlled, but the walls of the geometry are covered with human alveolar epithelial cells. By experimental observations and mathematical modelling of the draining film, it was shown that the rate of drainage is not only determined by the interfacial shear viscosity but also by the interfacial dilatational viscosity and the presence of Marangoni stresses. However, the experimental setup used did not allow to separate the different effects. As small surface tension gradients are sufficient to explain the observed results and can be reached with area changes similar as the ones during the elevation of the geometry, Marangoni stresses are most probable responsible for the observed drainage rates. For Survanta and HSA also their surface elasticity might play an important role. The presence of alveolar epithelial cells reduces drainage velocities even further due to surface roughness.In the third part of this study, the ability of lung surfactant surfaces to maintain a very low surface tensions and the corresponding high surface pressures, is studied. Four different mechanisms which could be responsible for a metastable high surface pressure are compared: the interfacial rheology, subphase rheology, diffusion limited sorption or slow sorption kinetics at the interface. Although information about the interfacial dilatational rheology is missing, the time scales and effect of bulk surfactant concentration indicate a sorption kinetics dominated mechanism. Adsorption/desorption kinetics are quantified by monitoring the restoration of the surface pressure towards the equilibrium value in time. The characteristic time scale of adsorption is strongly dependent on the bulk surfactant concentration. Whereas a timescale of approximately 30 s was observed in the experimental setup, it is expected that this value reduces to about 1.4 s for the concentration present in the lung. The rate of desorption is not much affected by concentration but the history of the monolayer may strongly determine the characteristic time scale for desorption. For a normal adsorbed layer the characteristic time scale for desorption is about 35 s. However, after successive compression/expansion cycles, similar to breathing, the desorption rate is reduced dramatically resulting in a metastable low surface tension. In addition, a regular repeat of a large expansion and compression, can postpones the loss of the metastable low surface tension. Finally, based on the fundamental insights in the interfacial dynamics of the main lung surfactant lipid DPPC and the lung surfactant replacements, combined with the expertise and observations of pulmonologists and biomedical scientists, it is possible to shed a new light on the functioning of lung surfactant. The adsorption/desorption kinetics might imply a vital importance of the human breathing pattern in order to maintain a metastable surfactant lining in the alveoli with a low surface tension. The low interfacial rheology in combination with moderate bulk rheological properties of the surfactant lining allow for significant Marangoni flows which might be important to avoid surfactant build up during breathing and sweep the alveolar surface clean on its way out.nrpages: 146status: publishe