Mechanistic Insights into Pulmonary Surfactant Inactivation.

Authors

Maria C Novaes-Silva, Mariana Rodríguez-Hakim, Jan Vermant

Published in

Langmuir : the ACS journal of surfaces and colloids. Jul 05, 2026. Epub Jul 05, 2026.

Abstract

Lung surfactant is essential for regulating alveolar surface stresses, reducing the work of breathing, maintaining compliance, and preventing collapse. Under pathological conditions such as acute respiratory distress syndrome (ARDS), this functionality is compromised, yet the underlying physical mechanisms remain incompletely understood. Recent work has shown that surfactant failure cannot be described from surface tension alone, but requires consideration of the interfacial dilatational modulus, which quantifies the ability of the interface to sustain stress under deformation. Mechanical instability arises when this stress-bearing capacity is lost, linking alveolar collapse directly to a reduction in the dilatational modulus. However, this response is typically interpreted in terms of equilibrium adsorption and Gibbs elasticity. Here, we demonstrate instead that it reflects the breakdown of nonequilibrium, microstructure-mediated mechanical surface stresses. By combining freestanding thin-film measurements, cryo-TEM imaging, and dilatational rheology, we isolate the effects of extra compressive stress contributions arising from interfacial microstructure and probe the effects of Albumin and lysophosphatidylcholine (LysoPC) on the clinical surfactant Infasurf. We show that LysoPC-induced structural reorganization disrupts the interfacial architecture, suppressing the development of compressive surface stresses and thereby weakening the mechanical integrity of the interface. These results establish a more subtle link between surfactant microstructure and the interfacial stress response, providing a physically grounded framework for surfactant inactivation and suggesting distinct directions for therapeutic design.

PMID:
42402027
Bibliographic data and abstract were imported from PubMed on 05 Jul 2026.

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