RT Journal Article
T1 Pulmonary surfactant lipid reorganization induced by the adsorption of the oligomeric surfactant protein B Complex
A1 Liekkinen, Juho
A1 Enkavi, Giray
A1 Javanainen, Matti
A1 Olmeda Lozano, Bárbara
A1 Pérez-Gil, Jesús
A1 Vattulainen, Ilpo
AB Surfactant protein B (SP-B) is essential in transferring surface-active phospholipids from membrane-based surfactant complexes into the alveolar air–liquid interface. This allows maintaining the mechanical stability of the surfactant film under high pressure at the end of expiration; therefore, SP-B is crucial in lung function. Despite its necessity, the structure and the mechanism of lipid transfer by SP-B have remained poorly characterized. Earlier, we proposed higher-order oligomerization of SP-B into ring-like supramolecular assemblies. In the present work, we used coarse-grained molecular dynamics simulations to elucidate how the ring-like oligomeric structure of SP-B determines its membrane binding and lipid transfer. In particular, we explored how SP-B interacts with specific surfactant lipids, and how consequently SP-B reorganizes its lipid environment to modulate the pulmonary surfactant structure and function. Based on these studies, there are specific lipid–protein interactions leading to perturbation and reorganization of pulmonary surfactant layers. Especially, we found compelling evidence that anionic phospholipids and cholesterol are needed or even crucial in the membrane binding and lipid transfer function of SP-B. Also, on the basis of the simulations, larger oligomers of SP-B catalyze lipid transfer between adjacent surfactant layers. Better understanding of the molecular mechanism of SP-B will help in the design of therapeutic SP-B-based preparations and novel treatments for fatal respiratory complications, such as the acute respiratory distress syndrome.
PB Elsevier
SN 0022-2836
YR 2020
FD 2020-05-02
LK https://hdl.handle.net/20.500.14352/6487
UL https://hdl.handle.net/20.500.14352/6487
LA eng
NO Ministerio de Ciencia e Innovación (MICINN)
NO Comunidad de Madrid
NO Sigrid Jusélius Foundation
NO Academy of Finland (Centre of Excellence program)
NO Helsinki Institute of Life Science
NO Emil Aaltonen Foundation
DS Docta Complutense
RD 10 abr 2025