(B-55) Extracting biophysical parameters of lung surfactant function from experimental pressure-area loops

Introduction:: Lung surfactant, a lipoprotein mixture that coats & stabilizes lung alveoli during breathing, modulates air-liquid surface tension and is critical for normal lung function. However, clinical evaluation of lung surfactant is challenging. Lung surfactant can be obtained from broncho-alveolar lavage (BAL) fluid, but biophysical analysis of BAL samples requires a surfactometer, a device that can oscillate droplets of BAL to create surface tension/pressure-area (P-A) hysteresis loops. Contemporary surfactometers, including the constrained drop surfactometer (CDS),¹ only characterize P-A loops via surface tension/pressure extrema and P-A loop area. However, these parameters are indirectly related to the biophysical properties of lung surfactant. Therefore, the goal of this study was to develop a CDS that can generate P-A loops from clinically relevant samples and to develop a computational model that can analyze these P-A loops to determine biophysical surfactant properties.


Materials and Methods:: Experimental CDS: Based on previous studies,¹ we constructed a CDS containing a sharp-edged droplet stage connected to a programmable syringe pump. A camera recorded videos of BAL droplets as they were oscillated at ~0.1 Hz. An in-house MATLAB code was used for axisymmetric droplet shape analysis¹ to produce surface tension-area loops (Figure 1A). For this study, BAL samples were obtained from wild-type BALC mice under conditions of spontaneous breathing (SB) or injurious mechanical ventilation (VILI) (e.g. high tidal volumes). Surface active large aggregates were isolated from BAL and resuspended in saline prior to analysis via the CDS.

Computational Model: The COMSOL finite element software package was used to simulate the CDS. First, multi-phase fluid moduli were used to solve the Stokes equations in an axisymmetric geometry with well-established air-liquid boundary conditions². Convection-diffusion equations were also solved to simulate surfactant transport and adsorption to the air-liquid interface. A linear equation of state was used to simulate surface tension changes due to surfactant adsorption.


Results, Conclusions, and Discussions:: Surface tension-area loops of spontaneously breathing and injured (VILI) mice exhibited qualitative differences. The interfacial area at which compression leads to dramatic lowering of surface tension was lower in injured compared to uninjured mice (Figure 1A). These differences were not captured by minimum surface tension vs cycle data (data not shown). Additionally, preliminary COMSOL simulations (Figure 1B) indicate that the computational model can simulate CDS dynamics at both high (72 mN/m) and low (10 mN/m) surface tensions.

We have developed an experimental CDS-based system that can generate P-A loops from clinically relevant samples and a computational model that can simulate the CDS experiment. Results indicate that global metrics such as minimum surface tension are limited, and we are currently integrating surfactant transport equations into computational simulations and using this integrated model to determine which biophysical parameters are altered during VILI.


Acknowledgements (Optional): :

References (Optional): : 1. Valle, R.P. et. al. 2015. ACS Nano. 9(5)5413-21. 2. Krueger, M. and D.P. Gaver III. 2000. J Coll Interface Sci. 229:353-64.