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Towards the Molecular Mechanism of Pulmonary Surfactant Protein SP-B: At the Crossroad of Membrane Permeability and Interfacial Lipid Transfer
Institution:1. Department of Biochemistry, Faculty of Biology, Complutense University, Madrid, Spain;2. Research Institute “Hospital 12 de Octubre (imas12)”, Complutense University, Madrid, Spain;1. Viral Recombination Section, HIV Dynamics and Replication Program, National Cancer Institute, Frederick, MD 21702, USA;2. Viral Mutation Section, HIV Dynamics and Replication Program, National Cancer Institute, Frederick, MD 21702, USA;1. Institute of Structural Biology, University of Bonn, 53127 Bonn, Germany;2. Physical and Synthetic Biology, Faculty of Biology, Ludwig-Maximilians-Universität München, 82152 Planegg-Martinsried, Germany;3. Molecular Microscopy Research Group, Zernike Institute for Advanced Materials, University of Groningen, Nijenborgh 4, 9747 AG Groningen, The Netherlands;4. Department of Biology (Area 10), University of York, York YO10 5YW, UK;1. Department of Cell Biology, Microbiology and Molecular Biology, University of South Florida, 4202 E. Fowler Ave., Tampa, FL 33620, USA;2. Physics and Materials Science Research Unit, University of Luxembourg, L-1511 Luxembourg, Luxembourg;3. Department of Physics, University of South Florida, 4202 E. Fowler Ave., Tampa, FL 33620, USA;1. Department of Bacteriology, The Jikei University School of Medicine, Minato-Ku, Tokyo 105-8461, Japan;2. Jikei Center for Biofilm Science and Technology, The Jikei University School of Medicine, Minato-Ku, Tokyo 105-8461, Japan;3. Department of Molecular Cell Biology, Institute of Molecular Embryology and Genetics, Kumamoto University, 2-2-1 Honjo, Chuo-Ku, Kumamoto 860-0811, Japan;4. Cell Biology Center, Institute of Innovative Research, Tokyo Institute of Technology, Midori-ku, Yokohama 226-8503, Japan;1. Division of Biomedical Convergence, College of Biomedical Science, Kangwon National University, Chuncheon 24341, Republic of Korea;2. Institute of Bioscience and Biotechnology, Kangwon National University, Chuncheon 24341, Republic of Korea;3. College of Veterinary Medicine, Kangwon National University, Chuncheon 24341, Republic of Korea;1. Departamento de Ciencia y Tecnología, Universidad Nacional de Quilmes, CONICET, Bernal, Buenos Aires, Argentina;2. Department of Biomedical Sciences, University of Padua, Padua, Italy;3. Sorbonne Université, CNRS, IBPS, Laboratoire de Biologie Computationnelle et Quantitative (LCQB), Paris, France
Abstract:Pulmonary surfactant is a lipid-protein complex that coats the alveolar air-liquid interface, enabling the proper functioning of lung mechanics. The hydrophobic surfactant protein SP-B, in particular, plays an indispensable role in promoting the rapid adsorption of phospholipids into the interface. For this, formation of SP-B ring-shaped assemblies seems to be important, as oligomerization could be required for the ability of the protein to generate membrane contacts and to mediate lipid transfer among surfactant structures. SP-B, together with the other hydrophobic surfactant protein SP-C, also promotes permeability of surfactant membranes to polar molecules although the molecular mechanisms underlying this property, as well as its relevance for the surface activity of the protein, remain undefined. In this work, the contribution of SP-B and SP-C to surfactant membrane permeability has been further investigated, by evaluation of the ability of differently-sized fluorescent polar probes to permeate through giant vesicles with different lipid/protein composition. Our results are consistent with the generation by SP-B of pores with defined size in surfactant membranes. Furthermore, incubation of surfactant with an anti-SP-B antibody not only blocked membrane permeability but also affected lipid transfer into the air-water interface, as observed in a captive bubble surfactometer device. Our findings include the identification of SP-C and anionic phospholipids as modulators required for maintaining native-like permeability features in pulmonary surfactant membranes. Proper permeability through membrane assemblies could be crucial to complement the overall role of surfactant in maintaining alveolar equilibrium, beyond its biophysical function in stabilizing the respiratory air-liquid interface.
Keywords:surfactant permeability  membrane pores  interfacial adsorption  fluorescent dextrans  giant vesicles  CBS"}  {"#name":"keyword"  "$":{"id":"k0035"}  "$$":[{"#name":"text"  "_":"captive bubble surfactometer  DOPE"}  {"#name":"keyword"  "$":{"id":"k0045"}  "$$":[{"#name":"text"  "_":"dioleoyl phosphatydilethanolamine  DPPC"}  {"#name":"keyword"  "$":{"id":"k0055"}  "$$":[{"#name":"text"  "_":"dipalmitoyl phosphatidylcholine  FITC"}  {"#name":"keyword"  "$":{"id":"k0065"}  "$$":[{"#name":"text"  "_":"fluorescein isothiocyanate  GV"}  {"#name":"keyword"  "$":{"id":"k0075"}  "$$":[{"#name":"text"  "_":"giant vesicle  LF"}  {"#name":"keyword"  "$":{"id":"k0085"}  "$$":[{"#name":"text"  "_":"lipid fraction of surfactant  OE"}  {"#name":"keyword"  "$":{"id":"k0095"}  "$$":[{"#name":"text"  "_":"organic extract of surfactant  PF"}  {"#name":"keyword"  "$":{"id":"k0105"}  "$$":[{"#name":"text"  "_":"hydrophobic protein fraction of surfactant  PG"}  {"#name":"keyword"  "$":{"id":"k0115"}  "$$":[{"#name":"text"  "_":"phosphatidylglycerol  POPC"}  {"#name":"keyword"  "$":{"id":"k0125"}  "$$":[{"#name":"text"  "_":"palmitoyl oleoyl phosphatydilcholine  POPG"}  {"#name":"keyword"  "$":{"id":"k0135"}  "$$":[{"#name":"text"  "_":"palmitoyl oleoyl phosphatydilglycerol  PS"}  {"#name":"keyword"  "$":{"id":"k0145"}  "$$":[{"#name":"text"  "_":"pulmonary surfactant  SP-A  SP-B  SP-C  SP-D"}  {"#name":"keyword"  "$":{"id":"k0155"}  "$$":[{"#name":"text"  "_":"surfactant proteins A  B  C and D
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