RT Journal Article T1 A small key unlocks a heavy door: the essential function of the small hydrophobic proteins SP-B and SP-C to trigger adsorption of pulmonary surfactant lamellar bodies A1 Hobi, Nina A1 Giolabi, Michael A1 Olmeda Lozano, Bárbara A1 Miklavc, Pika A1 Felder, Edward A1 Walter, Paul A1 Dietl, Paul A1 Frick, Manfred A1 Pérez-Gil, Jesús A1 Haller, Thomas AB The molecular basis involving adsorption of pulmonary surfactant at the respiratory air–liquid interface and the specific roles of the surfactant proteins SP-B and SP-C in this process have not been completely resolved. The reasons might be found in the largely unknown structural assembly in which surfactant lipids and proteins are released from alveolar type II cells, and the difficulties to sample, manipulate and visualize the adsorption of these micron-sized particles at an air–liquid interface under appropriate physiological conditions. Here, we introduce several approaches to overcome these problems. First, by immunofluorescence we could demonstrate the presence of SP-B and SP-C on the surface of exocytosed surfactant particles. Second, by sampling the released particles and probing their adsorptive capacity we could demonstrate a remarkably high rate of interfacial adsorption, whose rate and extent was dramatically affected by treatment with antibodies against SP-B and SP-C. The effect of both antibodies was additive and specific. Third, direct microscopy of an inverted air–liquid interface revealed that the blocking effect is due to a stabilization of the released particles when contacting the air–liquid interface, precluding their transformation and the formation of surface films. We conclude that SP-B and SP-C are acting as essential, preformed molecular keys in the initial stages of surfactant unpacking and surface film formation. We further propose that surfactant activation might be transduced by a conformational change of the surfactant proteins upon contact with surface forces acting on the air–liquid interface. PB Elsevier SN 0006-3002 YR 2016 FD 2016-08 LK https://hdl.handle.net/20.500.14352/17877 UL https://hdl.handle.net/20.500.14352/17877 LA eng NO Ministerio de Economía y Competitividad (MINECO) NO Comunidad de Madrid NO Ulm University (Holanda)-Bausteinprogram NO Carl Zeiss Foundation (Alemania) DS Docta Complutense RD 7 abr 2025