biostudies-literatureFisher JMNational Heart, Lung, and Blood InstituteNHLBI NIH HHS7321-7332https://www.ebi.ac.uk/biostudies/studies/S-EPMC11530962biostudies-literatureUnknown20(36)Lung surfactant is inactivated in acute respiratory distress syndrome (ARDS) by a mechanism that remains unclear. Phospholipase (PLA₂) plays an essential role in the normal lipid recycling processes, but is present in elevated levels in ARDS, suggesting it plays a role in ARDS pathophysiology. PLA₂ hydrolyzes lipids such as DPPC-the primary component of lung surfactant-into palmitic acid (PA) and lyso-PC (LPC). Because PA co-crystallizes with DPPC to form rigid, elastic domains, we hypothesize that PLA₂-catalyzed degradation establishes a stiff, heterogeneous rheology in the monolayer, and suggests a potential mechanical role in disrupting lung surfactant function during ARDS. Here we study the morphological and rheological changes of DPPC monolayers as they are degraded by PLA₂ using interfacial microbutton microrheometry coupled with fluorescence microscopy. While degrading, domain morphology passes through qualitatively distinct transitions: compactification, coarsening, solidification, aggregation, network percolation, network erosion, and nucleation of PLA₂-rich domains. Initially, condensed domains relax to more compact shapes, and coarsen <i>via</i> Ostwald ripening and coalescence up until the domains solidify, marked by a distinct roughening of domain boundaries that does not relax. Domains aggregate and eventually form a percolated network, whose elements then erode and whose connections are broken as degradation continues. The relative enzymatic activity of PLA₂, set by the age of the sample, impacts the order and the duration of morphology transitions. The fresher the PLA₂, the faster the overall degradation, and the earlier the onset of domain solidification: domains solidify before aggregating with fresh PLA₂ samples, but aggregate and percolate before solidification with aged PLA₂. Irrespective of the activity of the PLA₂, all measured linear viscoelastic surface shear moduli obey the same dependence on condensed phase area fraction (log|<i>G</i>*| ∝ <i>ϕ</i>) throughout monolayer degradation. Moreover, the onset of domain solidification coincides with the time when the relative surface elasticity begins to increase.Soft matterPhospholipase-catalyzed degradation drives domain morphology and rheology transitions in model lung surfactant monolayers.PMC11530962R01 HL135065R01 HL051177R01 HL51177Squires TMFisher JMfalsePhospholipase-catalyzed degradation drives domain morphology and rheology transitions in model lung surfactant monolayers.Lung surfactant is inactivated in acute respiratory distress syndrome (ARDS) by a mechanism that remains unclear. Phospholipase (PLA₂) plays an essential role in the normal lipid recycling processes, but is present in elevated levels in ARDS, suggesting it plays a role in ARDS pathophysiology. PLA₂ hydrolyzes lipids such as DPPC-the primary component of lung surfactant-into palmitic acid (PA) and lyso-PC (LPC). Because PA co-crystallizes with DPPC to form rigid, elastic domains, we hypothesize that PLA₂-catalyzed degradation establishes a stiff, heterogeneous rheology in the monolayer, and suggests a potential mechanical role in disrupting lung surfactant function during ARDS. Here we study the morphological and rheological changes of DPPC monolayers as they are degraded by PLA₂ using interfacial microbutton microrheometry coupled with fluorescence microscopy. While degrading, domain morphology passes through qualitatively distinct transitions: compactification, coarsening, solidification, aggregation, network percolation, network erosion, and nucleation of PLA₂-rich domains. Initially, condensed domains relax to more compact shapes, and coarsen <i>via</i> Ostwald ripening and coalescence up until the domains solidify, marked by a distinct roughening of domain boundaries that does not relax. Domains aggregate and eventually form a percolated network, whose elements then erode and whose connections are broken as degradation continues. The relative enzymatic activity of PLA₂, set by the age of the sample, impacts the order and the duration of morphology transitions. The fresher the PLA₂, the faster the overall degradation, and the earlier the onset of domain solidification: domains solidify before aggregating with fresh PLA₂ samples, but aggregate and percolate before solidification with aged PLA₂. Irrespective of the activity of the PLA₂, all measured linear viscoelastic surface shear moduli obey the same dependence on condensed phase area fraction (log|<i>G</i>*| ∝ <i>ϕ</i>) throughout monolayer degradation. Moreover, the onset of domain solidification coincides with the time when the relative surface elasticity begins to increase.2024-01-01T00:00:00Z2024 Sep2026-06-02T09:38:57.736Z2026-05-26T03:06:38.85ZS-EPMC115309623924849710.1039/d4sm00306c