Department of Chemical Engineering, University of California Santa Barbara, Santa Barbara, CA 93106, USA.
Soft Matter. 2024 Sep 18;20(36):7321-7332. doi: 10.1039/d4sm00306c.
Lung surfactant is inactivated in acute respiratory distress syndrome (ARDS) by a mechanism that remains unclear. Phospholipase (PLA) 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 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-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 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-rich domains. Initially, condensed domains relax to more compact shapes, and coarsen 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, set by the age of the sample, impacts the order and the duration of morphology transitions. The fresher the PLA, the faster the overall degradation, and the earlier the onset of domain solidification: domains solidify before aggregating with fresh PLA samples, but aggregate and percolate before solidification with aged PLA. Irrespective of the activity of the PLA, all measured linear viscoelastic surface shear moduli obey the same dependence on condensed phase area fraction (log|*| ∝ ) throughout monolayer degradation. Moreover, the onset of domain solidification coincides with the time when the relative surface elasticity begins to increase.
肺表面活性剂在急性呼吸窘迫综合征（ARDS）中失活的机制尚不清楚。磷脂酶（PLA）在正常的脂质循环过程中起着至关重要的作用，但在 ARDS 中其水平升高，这表明它在 ARDS 的病理生理学中起作用。PLA 将 DPPC 等脂质（肺表面活性剂的主要成分）水解为棕榈酸（PA）和溶血性磷脂酰胆碱（LPC）。由于 PA 与 DPPC 共结晶形成刚性、有弹性的域，我们假设 PLA 催化的降解在单层中建立了刚性、不均匀的流变学，这表明在 ARDS 期间破坏肺表面活性剂功能的潜在机械作用。在这里，我们使用界面微按钮微流变仪结合荧光显微镜研究 DPPC 单层在 PLA 降解过程中的形态和流变变化。在降解过程中，域形态经历了定性上不同的转变：致密化、粗化、固化、聚集、网络渗流、网络侵蚀和 PLA 丰富域的成核。最初，凝聚的域松弛到更紧凑的形状，并通过 Ostwald 熟化和聚结粗化，直到域固化，域边界的明显粗糙化不松弛为标志。域聚集并最终形成一个渗流网络，其元素随后侵蚀，并且随着降解的继续，其连接被打破。PLA 的相对酶活性（由样品的年龄决定）影响形态转变的顺序和持续时间。PLA 越新鲜，整体降解速度越快，域固化的开始越早：与新鲜 PLA 样品相比，域在聚集之前就固化，但与老化 PLA 相比，域在聚集和渗流之前就固化。无论 PLA 的活性如何，在整个单层降解过程中，所有测量的线性粘弹性表面剪切模量都遵循相同的凝聚相面积分数依赖性（log|*|∝）。此外，域固化的开始与相对表面弹性开始增加的时间一致。
