2026-06-28T20:05:02Zhttps://docta.ucm.es/rest/oai/request
oai:docta.ucm.es:20.500.14352/1340252026-03-17T01:10:47Zcom_20.500.14352_14col_20.500.14352_15
Docta Complutense author Chichón, Francisco Javier author Cerrada, Alejandro author Arranz, Rocío author Cruz Rodríguez, Antonio author Valpuesta, José María author Pérez Gil, Jesús 2026-03-16T14:25:37Z 2026-03-16T14:25:37Z 2025-12-02 Chichon, F. J., Cerrada, A., Arranz, R., Cruz, A., Valpuesta, J. M., & Perez-Gil, J. (2026). Novel ultrastructural insights in lung surfactant membrane complexes under closer-to-native conditions as revealed by cryo-microscopy techniques. American Journal of Physiology-Lung Cellular and Molecular Physiology, 330(2), L105-L114. https://doi.org/10.1152/ajplung.00241.2025 1040-0605 10.1152/ajplung.00241.2025 https://hdl.handle.net/20.500.14352/134025 1522-1504 https://doi.org/10.1152/ajplung.00241.2025 Lung surfactant (LS) plays an essential role in preventing lung collapse due to physical forces by forming surface-active lipid-protein membranous films at the respiratory air-liquid interface. Throughout its biological cycle, LS exists in a variety of metabolically related, conspicuous morphological forms. Epithelial alveolar type II cells store LS as intracellular, tightly packed, multilayered organelles known as lamellar bodies. These are secreted as still-condensed material in the form of lamellar body-like particles, which, upon adsorption, give rise to the interfacial film and surface-associated structures. Surfactant material purified from bronchoalveolar lavage fluids has been extensively examined by conventional transmission electron microscopy (TEM), providing important information about LS ultrastructure. However, potential artifacts associated with classical TEM preparation methods—such as staining, dehydration, resin embedding, and sectioning—hinder the observation of surfactant biological samples in their truly native state. In this work, we have taken advantage of cutting-edge cryo-microscopy techniques to visualize the structural complexity present in LS preparations without fixation, in a frozen-hydrated state, and thus closer to physiological conditions. The implementation of cryopreservation approaches has allowed us to unveil unprecedented ultrastructural details of the diverse morphological states in which LS is present in the alveolar spaces, such as the presence of a protein-based pore connecting the lumen of the lamellar body-like particles (LBPs) with the external milieu, and an onion-like structure that suggests a mechanism that uses the energy accumulated upon LB assembly in the pneumocytes for a rapid release of the membranous complexes to the exterior. These morphological features shed light on the dynamic processes by which LS is unpacked from secreted condensed states to the more disorganized, interconnected membranous networks that sustain breathing mechanics. eng Attribution-NonCommercial-NoDerivatives 4.0 International Novel ultrastructural insights in lung surfactant membrane complexes under closer-to-native conditions as revealed by cryo-microscopy techniques journal article UGFyYSBxdWUgZWwgcmVwb3NpdG9yaW8gaW5zdGl0dWNpb25hbCBkZSBsYSBVbml2ZXJzaWRhZCBkZSBNYWRyaWQgcHVlZGEgYWxtYWNlbmFyIHkgZGlzdHJpYnVpciBlbCBvYmpldG8gZGlnaXRhbCBkZXBvc2l0YWRvLCBlcyBuZWNlc2FyaW8gcXVlIGxhIHBlcnNvbmEgcXVlIGhhZ2EgZWwgZGVww7NzaXRvIGxlYSB5IGFjZXB0ZSBsYXMgY29uZGljaW9uZXMgZXN0YWJsZWNpZGFzIGVuIGVzdGEgbGljZW5jaWE6CuKAoiBBY2VwdGFuZG8gZXN0YSBsaWNlbmNpYSwgdXN0ZWQgY29tbyBhdXRvci9yZXMgeS9vIHByb3BpZXRhcmlvL3MgZGUgbG9zIGRlcmVjaG9zIGRlIHByb3BpZWRhZCBpbnRlbGVjdHVhbCwgbyBsYSBwZXJzb25hIGRlbGVnYWRhIHBhcmEgaGFjZXJsbyAsIG90b3JnYSBhbCByZXBvc2l0b3JpbyBkZSBsYSBVbml2ZXJzaWRhZCBDb21wbHV0ZW5zZSBkZSBNYWRyaWQgZWwgZGVyZWNobyBubyBleGNsdXNpdm8gZGUgcmVwcm9kdWNjacOzbiB5IGRpc3RyaWJ1Y2nDs24gZGUgc3Ugb2JyYSBlbiBjdWFscXVpZXIgZm9ybWF0byB5IG1lZGlvLgrigKIgRWwgZGVwb3NpdGFudGUsIGVuIGNhc28gZGUgdW5hIG9icmEgY29uIG3DoXMgZGUgdW4gYXV0b3IsIGdhcmFudGl6YSBxdWUgbG8gaGFjZSByZXNwb25zYWJsZW1lbnRlIGVuIG5vbWJyZSB5IGNvbiBjb25zZW50aW1pZW50byBkZSBsb3MgZGVtw6FzIGF1dG9yZXMuCuKAoiBBY2VwdGEgcXVlIGVsIHJlcG9zaXRvcmlvIGRlIGxhIFVuaXZlcnNpZGFkIENvbXBsdXRlbnNlIGRlIE1hZHJpZCBwdWVkYSBjb25zZXJ2YXIgbcOhcyBkZSB1bmEgY29waWEgZGUgZXN0ZSBkb2N1bWVudG8geSwgc2luIGFsdGVyYXIgc3UgY29udGVuaWRvLCBjb252ZXJ0aXJsbyBhIGN1YWxxdWllciBmb3JtYXRvIGRlIGZpY2hlcm8sIG1lZGlvIG8gc29wb3J0ZSwgcGFyYSBwcm9ww7NzaXRvcyBkZSBzZWd1cmlkYWQgeSBwcmVzZXJ2YWNpw7NuLgrigKIgRGVjbGFyYSBxdWUgZWwgZG9jdW1lbnRvIGVzIHVuIHRyYWJham8gb3JpZ2luYWwgc3V5bywgbyBxdWUgZXMgbGEgcGVyc29uYSBkZWxlZ2FkYSBwYXJhIHJlYWxpemFyIGVsIGRlcMOzc2l0byB5LCBwb3IgdGFudG8sIGN1ZW50YSBjb24gbGEgcG90ZXN0YWQgcGFyYSBvdG9yZ2FyIGxvcyBkZXJlY2hvcyBjb250ZW5pZG9zIGVuIGVzdGEgbGljZW5jaWEuIFRhbWJpw6luIGRlY2xhcmEgcXVlIHN1IGRvY3VtZW50byBubyBpbmZyaW5nZSBsbyBlc3RhYmxlY2lkbyBlbiBsYSB2aWdlbnRlIGxlZ2lzbGFjacOzbiBkZSBwcm9waWVkYWQgaW50ZWxlY3R1YWwuCuKAoiBTaSBlbCBkb2N1bWVudG8gY29udGllbmUgbWF0ZXJpYWxlcyBkZSBsb3MgY3VhbGVzIG5vIHRpZW5lIGxvcyBkZXJlY2hvcyBkZSBhdXRvciwgZGVjbGFyYSBxdWUgaGEgb2J0ZW5pZG8gZWwgcGVybWlzbyBzaW4gcmVzdHJpY2Npw7NuIGRlbCBwcm9waWV0YXJpbyBwYXJhIG90b3JnYXIgYSBsYSBVbml2ZXJzaWRhZCBDb21wbHV0ZW5zZSBkZSBNYWRyaWQgbG9zIGRlcmVjaG9zIHJlcXVlcmlkb3MgcG9yIGVzdGEgbGljZW5jaWEsIHkgcXVlIGVzZSBtYXRlcmlhbCwgY3V5b3MgZGVyZWNob3Mgc29uIGRlIHRlcmNlcm9zLCBlc3TDoSBjbGFyYW1lbnRlIGlkZW50aWZpY2FkbyB5IHJlY29ub2NpZG8gZGVudHJvIGRlbCBjb250ZW5pZG8gZGVsIGRvY3VtZW50by4K4oCiIFNpIGVsIGRvY3VtZW50byBzZSBiYXNhIGVuIHVuYSBvYnJhIHF1ZSBoYSBzaWRvIHBhdHJvY2luYWRhIG8gYXBveWFkYSBwb3IgdW5hIGFnZW5jaWEgdSBvcmdhbml6YWNpw7NuIGRpZmVyZW50ZSBkZSBsYSBVbml2ZXJzaWRhZCBDb21wbHV0ZW5zZSBkZSBNYWRyaWQsIHVzdGVkIGRlY2xhcmEgcXVlIGhhIGN1bXBsaWRvIGNvbiBsYXMgb2JsaWdhY2lvbmVzIHJlcXVlcmlkYXMgcG9yIGVzdGUgY29udHJhdG8gbyBhY3VlcmRvLgrigKIgTGEgVW5pdmVyc2lkYWQgQ29tcGx1dGVuc2UgZGUgTWFkcmlkIGlkZW50aWZpY2Fyw6EgY2xhcmFtZW50ZSBzdS9zIG5vbWJyZS9zIGNvbW8gZWwvbG9zIGF1dG9yL2VzIG8gcHJvcGlldGFyaW8vcyBkZSBsb3MgZGVyZWNob3MgZGVsIGRvY3VtZW50bywgeSBubyBoYXLDoSBuaW5ndW5hIGFsdGVyYWNpw7NuIGRlIHN1IGRvY3VtZW50byBkaWZlcmVudGUgYSBsYXMgcGVybWl0aWRhcyBlbiBlc3RhIGxpY2VuY2lhLgrigKIgVHJhYmFqb3MgZGVwb3NpdGFkb3MgcG9yIHN1IHByb3BpbyBhdXRvcjogYWwgYXV0by1hcmNoaXZhciBlc3RhIGNvbGVjY2nDs24gZGUgZmljaGVyb3MgeSBtZXRhZGF0b3MgYmlibGlvZ3LDoWZpY29zIGFzb2NpYWRvcywgb3RvcmdvIGFsIHJlcG9zaXRvcmlvIGluc3RpdHVjaW9uYWwgZGUgbGEgVW5pdmVyc2lkYWQgQ29tcGx1dGVuc2UgZGUgTWFkcmlkIGVsIGRlcmVjaG8gcGFyYSBhbG1hY2VuYXJsb3MgeSBkaXN0cmlidWlybG9zLiBEZWNsYXJvIHF1ZSBlc3RlIG1hdGVyaWFsIGVzIGRlIG1pIHByb3BpZWRhZCBpbnRlbGVjdHVhbCB5IHF1ZSBlbCByZXBvc2l0b3JpbyBpbnN0aXR1dGljaW9uYWwgZGUgbGEgVW5pdmVyc2lkYWQgQ29tcGx1dGVuc2UgZGUgTWFkcmlkLCBubyBhc3VtZSByZXNwb25zYWJpbGlkYWQgYWxndW5hIGVuIGNhc28gZGUgcXVlIHNlIHByb2R1emNhIHVuYSB2aW9sYWNpw7NuIGRlIGRlcmVjaG9zIGRlIHByb3BpZWRhZCBhbCBkaXN0cmlidWlyIGVzdG9zIGZpY2hlcm9zIG8gbWV0YWRhdG9zLgrigKIgVHJhYmFqb3MgZGVwb3NpdGFkb3MgcG9yIG90cm9zIHF1ZSBubyBzZWFuIHN1IGF1dG9yOiBkZWNsYXJvIHF1ZSBsb3MgbWV0YWRhdG9zIGJpYmxpb2dyw6FmaWNvcyBxdWUgZXN0b3kgYXJjaGl2YW5kbyBlbiBlbCByZXBvc2l0b3JpbyBpbnN0aXR1Y2lvbmFsIGRlIGxhIFVuaXZlcnNpZGFkIENvbXBsdXRlbnNlIGRlIE1hZHJpZCwgc29uIGRlIGRvbWluaW8gcMO6YmxpY28uIFNpIG5vIGZ1ZXNlIGVsIGNhc28sIGFjZXB0byBwbGVuYSByZXNwb25zYWJpbGlkYWQgcG9yIGN1YWxxdWllciBpbmZyYWNjacOzbiBkZSBkZXJlY2hvcyBkZSBhdXRvciBxdWUgY29ubGxldmUgbGEgZGlzdHJpYnVjacOzbiBkZSBlc3RvcyBmaWNoZXJvcyBvIG1ldGFkYXRvcy4K4oCiIFBvciB0YW50bywgdG9kb3MgbG9zIG1ldGFkYXRvcyBwdWJsaWNhZG9zIGVuIGVsIHJlcG9zaXRvcmlvIGluc3RpdHVjaW9uYWwgZGUgbGEgVW5pdmVyc2lkYWQgQ29tcGx1dGVuc2UgZGUgTWFkcmlkLCBlc3TDoW4gZGlzcG9uaWJsZXMgY29uIGxhIGxpY2VuY2lhIENyZWF0aXZlIENvbW1vbnMgQ0MwIDEuMCBVbml2ZXJzYWwgT2ZyZWNpbWllbnRvIGFsIERvbWluaW8gUMO6YmxpY28gKENDMCAxLjApLiBFc3RhIGxpY2VuY2lhIHBlcm1pdGUgY29waWFyLCBtb2RpZmljYXIsIGRpc3RyaWJ1aXIsIHJldXRpbGl6YXIgeSBjb21wYXJ0aXIgcMO6YmxpY2EgeSBsaWJyZW1lbnRlIGxvcyBtZXRhZGF0b3MgKGluY2x1eWVuZG8gc3UgdXNvIGNvbWVyY2lhbCksIHNpbiB0ZW5lciBxdWUgcGVkaXIgcGVybWlzby4gU2kgdGVyY2VyYXMgcGFydGVzIHVzYW4gZXN0b3MgbWV0YWRhdG9zLCBkZWJlbiBoYWNlciB1biByZWNvbm9jaW1pZW50byB5IHVuYSBhdHJpYnVjacOzbiBhIGxhcyBmdWVudGVzIGRlIGxvcyBtaXNtb3MuIExhIHJldXRpbGl6YWNpw7NuIGRlIGVzdG9zIG1ldGFkYXRvcyB0YW1iacOpbiBlcyBsaWJyZSwgdGFsIHkgY29tbyBlc3RhYmxlY2UgbGEgbGljZW5jaWEgZGUgdXNvIENDMC4K URL https://docta.ucm.es/bitstreams/6846472c-95e3-453a-8978-9d6de7a65eb0/download File MD5 6d6a37009a44441561c3f9133e63301a 3811311 application/pdf chichón-et-al-2026-novel-ultrastructural-insights-in-lung-surfactant-membrane-complexes-under-closer-to-native.pdf