{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Fisher JM"],"funding":["National Heart, Lung, and Blood Institute","NHLBI NIH HHS"],"pagination":["7321-7332"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11530962"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["20(36)"],"pubmed_abstract":["Lung surfactant is inactivated in acute respiratory distress syndrome (ARDS) by a mechanism that remains unclear. Phospholipase (PLA<sub>2</sub>) 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. PLA<sub>2</sub> 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 PLA<sub>2</sub>-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 PLA<sub>2</sub> 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 PLA<sub>2</sub>-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 PLA<sub>2</sub>, set by the age of the sample, impacts the order and the duration of morphology transitions. The fresher the PLA<sub>2</sub>, the faster the overall degradation, and the earlier the onset of domain solidification: domains solidify before aggregating with fresh PLA<sub>2</sub> samples, but aggregate and percolate before solidification with aged PLA<sub>2</sub>. Irrespective of the activity of the PLA<sub>2</sub>, 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."],"journal":["Soft matter"],"pubmed_title":["Phospholipase-catalyzed degradation drives domain morphology and rheology transitions in model lung surfactant monolayers."],"pmcid":["PMC11530962"],"funding_grant_id":["R01 HL135065","R01 HL051177","R01 HL51177"],"pubmed_authors":["Squires TM","Fisher JM"],"additional_accession":[]},"is_claimable":false,"name":"Phospholipase-catalyzed degradation drives domain morphology and rheology transitions in model lung surfactant monolayers.","description":"Lung surfactant is inactivated in acute respiratory distress syndrome (ARDS) by a mechanism that remains unclear. Phospholipase (PLA<sub>2</sub>) 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. PLA<sub>2</sub> 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 PLA<sub>2</sub>-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 PLA<sub>2</sub> 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 PLA<sub>2</sub>-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 PLA<sub>2</sub>, set by the age of the sample, impacts the order and the duration of morphology transitions. The fresher the PLA<sub>2</sub>, the faster the overall degradation, and the earlier the onset of domain solidification: domains solidify before aggregating with fresh PLA<sub>2</sub> samples, but aggregate and percolate before solidification with aged PLA<sub>2</sub>. Irrespective of the activity of the PLA<sub>2</sub>, 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.","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Sep","modification":"2026-06-02T09:38:57.736Z","creation":"2026-05-26T03:06:38.85Z"},"accession":"S-EPMC11530962","cross_references":{"pubmed":["39248497"],"doi":["10.1039/d4sm00306c"]}}