Simulated Breathing: Application of Molecular Dynamics Simulations to Pulmonary Lung Surfactant

Basel Mansour,Maksymilian Dziura,Mitchell DiPasquale,James W. Gauld,Drew Marquardt,P. Charukeshi Chandrasekera

doi:10.3390/sym13071259

Abstract

In this review, we delve into the topic of the pulmonary surfactant (PS) system, which is present in the respiratory system. The total composition of the PS has been presented and explored, from the types of cells involved in its synthesis and secretion, down to the specific building blocks used, such as the various lipid and protein components. The lipid and protein composition varies across species and between individuals, but ultimately produces a PS monolayer with the same role. As such, the composition has been investigated for the ways in which it imposes function and confers peculiar biophysical characteristics to the system as a whole. Moreover, a couple of theories/models that are associated with the functions of PS have been addressed. Finally, molecular dynamic (MD) simulations of pulmonary surfactant have been emphasized to not only showcase various group’s findings, but also to demonstrate the validity and importance that MD simulations can have in future research exploring the PS monolayer system.

Highlights

Often unheralded, lipids play an integral role in many aspects of life, in physiology
This selective exclusion permits a greater proportion of the monolayer to be in a liquid-condensed (LC) phases enriched in DPPC, the main lipid responsible for achieving very low surface tensions
It has been suggested that during squeeze-out, the N-terminal palmitate groups of surfactant proteins (SP)-C can remain anchored in the interfacial monolayer, while the transmembrane helical domain is expelled with a group of associated lipids, forming the multilayer reservoirs

Summary

Introduction

Lipids play an integral role in many aspects of life, in physiology. Pulmonary surfactant (PS) is a critical lipid-protein complex within the respiratory system [1] It is involved in many different functions, such as increasing lung compliance, preventing alveolar collapse, and even as an initial immunological defense. The film is a monolayer system in the alveolar cavity that forms an air-liquid interface, with the hydrophobic fatty acid tails facing the air, and the hydrophilic heads with an orientation towards the aqueous subphase.

Surfactant Composition

Cholesterol

Surfactant Proteins

Hydrophilic Proteins

Hydrophobic Proteins

Surfactant Function

Role of Oxidative Stress

Supercompression Model

Molecular Dynamics

Tuning the Phase Transition

Looking beyond the Interface

Supercompression through the In Silico Lens