First resolution of the structure of lung surfactant reservoirs at near zero surface tension and their inhibition by serum proteins

The structure of lung surfactant reservoirs, from which surfactant protein assists the resupply of lipid back to the surface monolayer to maintain low surface tension during expiration, has not been resolved experimentally to date. In our lab, we have been studying model lung surfactant systems held at surface pressures of 70 mN/m, close to zero surface tension, to understand the effect of peptide-mediated lipid transport at the air/water interface. A recent neutron reflectivity experiment on INTER allowed us to resolve the lipid reservoirs, but the experimental objectives were left incomplete due to 2 days of lost time, and the most novel measurements at 70 mN/m and using selective deuteration to resolve which component is expelled into the reservoir were not acquired. We have gone on to investigate effects of the serum protein fibrinogen on the inhibition of lung function, which is of relevance to acute respiratory distress syndrome experienced by patients as a result of COVID-19. This proposal aims to complete the measurements on reservoir structures with respect to the presence of Mini-B peptide and extend the study to fibrinogen interactions at a range of surface pressures. It is expected that the research, part of a final year PhD student's thesis, will result in two timely and high impact publications.