Abstract: The delicate alveolar structure of the mammalian lungs is stabilized against forces tending to its collapse, thanks to the coating of a complex lipid-protein network assembled by the pulmonary surfactant system. This material, assembled and secreted by type II pneumocytes, prevents the exposure to air of the thin layer of fluid wetting the large respiratory surface, thus reducing surface tension close to 0 mN/m at the end of expiration. Lack of this material, or its deactivation as a consequence of inflammation and lung injury is associated with toxicity by inhalation and with severe respiratory pathologies. The physiological action of surfactant critically depends of a proper composition consisting of 90% by mass of lipids and less than 10% of specific proteins that impart to lipids unique dynamic properties. The interaction of inhaled entities (pollutants, particles, microorganisms, allergens, drugs) with the air-exposed surfactant coating of the airways defines their fate and action upon either spreading towards the deep lung or clearance through the mucociliary scalator of the upper airways. We have developed different in vitro and ex vivo models that capture essential alveolar geometries, breathing-like dynamics and cellular complexities of the respiratory surface. We have used these models to characterize the molecular mechanisms of pulmonary surfactant, the impact of the interaction of surfactant with inhaled toxics, particles and drugs, and the potential therapeutic utility of surfactant-related products. Lipid-protein interactions optimized in minimal surfactant models capture the essential properties of this material and are leading to the design and production of a novel generation of clinical surfactants useful both to treat important respiratory pathologies and to facilitate the delivery of inhaled drugs or nanoparticles.
Prof. Jesús Pérez-Gil is full professor in the department of biochemistry and molecular biology at Universidad Complutense de Madrid (UCM) where he leads a research group o the biophysics of membranes and lipid-protein interfaces (http://www.bb1.ucm.es/biomil/). He is also director of the consortium BIOPHYS-Hub (Biophysics for Biotechnology and Biomedicine; https://bibliometria.ucm.es/fichaGrupo/dp/862). He was previously chair of the department of biochemistry and molecular biology and dean of the biology faculty, both at UCM. He is member of the Spanish Biophysical Society, Spanish Biochemical Society, American Biophysical Society, and European Biophysical Societies Academy as well as member of the editorial board of Biochimica Biophysica Acta – Biomembranes and editor-in-chief of Chemistry and Physics of Lipids. His research interests span the molecular mechanisms at the respiratory surface: respiratory physiology, breathing mechanics, innate defence at the airways, inhaled drug delivery, and pulmonary toxicity.