Cañadas Benito, OlgaGarcía Verdugo, IgnacioKeough, KevinCasals Carro, María CristinaAxelsen, Paul2024-01-152024-01-152008Cañadas O, García-Verdugo I, Keough KM, Casals C. 2008. SP-A permeabilizes lipopolysaccharide membranes by forming protein aggregates that extract lipids from the membrane. Biophys. J. 2008 Oct; 95(7): 3287-940006-349510.1529/biophysj.108.137323https://hdl.handle.net/20.500.14352/93210Surfactant protein A (SP-A) is known to cause bacterial permeabilization. The aim of this work was to gain insight into the mechanism by which SP-A induces permeabilization of rough lipopolysaccharide (Re-LPS) membranes. In the presence of calcium, large interconnected aggregates of fluorescently labeled TR-SP-A were observed on the surface of Re-LPS films by epifluorescence microscopy. Using Re-LPS monolayer relaxation experiments at constant surface pressure, we demonstrated that SP-A induced Re-LPS molecular loss by promoting the formation of three-dimensional lipid-protein aggregates in Re-LPS membranes. This resulted in decreased van der Waals interactions between Re-LPS acyl chains, as determined by differential scanning calorimetry, which rendered the membrane leaky. We also showed that the coexistence of gel and fluid lipid phases within the Re-LPS membrane conferred susceptibility to SP-A-mediated permeabilization. Taken together, our results seem to indicate that the calcium-dependent permeabilization of Re-LPS membranes by SP-A is related to the extraction of LPS molecules from the membrane due to the formation of calcium-mediated protein aggregates that contain LPS.engjournal article1542-0086https://doi.org/10.1529/biophysj.108.137323open access577.112612.2Bioquímica (Biología)Fisiología2302 Bioquímica2411.17 Fisiología de la Respiración