Temperature-Dependent Mechanical and Phase Behavior of Pulmonary Surfactant Monolayers Studied by Dissipative Particle Dynamics Modeling and Experiments

Langmuir monolayers of dipalmitoyl phosphatidylcholine (DPPC) at air-water interfaces exhibit complex phase behavior important for pulmonary surfactant function. Despite extensive experimental and computational studies, accurately predicting their temperature-dependent properties remains challenging due to experimental limitations and computational constraints. Here, we present a novel coarse-grained computational approach using dissipative particle dynamics (DPD) that successfully reproduces the interfacial and mechanical properties of DPPC monolayers across physiologically relevant temperatures. We developed a DPD gas model with exponential repulsive potentials to simulate the air-water interface, coupled with a systematic temperature scaling methodology that enables parameter transferability across different temperatures. Our model accurately captures the air-water surface tension over a broad temperature range and reproduces experimental surface pressure-area isotherms of DPPC monolayers in quantitative agreement at 293K and within experimental uncertainty at higher temperatures. The simulations reveal detailed insights into the liquid condensed (LC) and liquid expanded (LE) phase coexistence, characterized by local thickness variations and lipid tail orientational order. At low temperatures, we observe distinct LC domains with highly ordered lipid tails coexisting with LE domains, which progressively diminish in size and mix with LE phases as temperature increases toward the critical point. Complementary experimental measurements using a temperature-controlled Langmuir trough and atomic force microscopy (AFM) confirm these phase transitions and domain formations, providing direct visualization of temperature-dependent morphological changes in DPPC monolayers. The model successfully predicts the temperature-dependent structural transitions in both monolayers and bilayers, including the gel-to-liquid crystalline phase transition, with equilibrium properties matching experimental measurements. This computationally efficient approach provides a robust framework for investigating complex surfactant systems and their interactions with nanoparticles, with broad implications for understanding pulmonary surfactant function and dysfunction in respiratory diseases.