Surface Behaviour of Peptoid Mimics of Pulmonary Surfactant Protein SP-C: Captive Bubble Surfactometry

Abstract

Pulmonary surfactant lipopeptide SP-C modulates the surface properties of interfacial films required to stabilize the respiratory interface along breathing dynamics. Several attempts have been made to produce entirely synthetic analogs of SP-C suitable to develop potentially useful therapeutic preparations.In this study we have tested the potential of five different poly-N-substituted glycines, or peptoids, designed to mimic (roughly) the primary and secondary structure and hydrophobicity of SP-C, to produce acceptable surfactant-like behaviour once incorporated into lipid/peptoid suspensions and assessed in a captive bubble surfactometer (CBS). The surface activities of different peptoids were compared in two model lipid mixtures: DPPC/POPG/Palmitic acid (68/22/9), which resembles the lipid composition of several clinical surfactants currently in use, and DPPC/POPC/POPG/Chol (50/25/15/10), which mimics the balance of saturated/unsaturated and zwitterionic/anionic phospholipids and the cholesterol content of natural surfactant as purified from bronchoalveolar lavage. We have assessed the ability of the different lipid/peptoid suspensions to i) rapidly adsorb at the bubble air-liquid interface, ii) stably produce very low surface tensions upon relatively slow repetitive quasi-static compressions and iii) maintain the lowest surface tensions with minimal compression and hysteresis under rapid physiological-like compression-expansion dynamics. Significant differences were found between different peptoids differing in their backbone structure and hydrophobicity, with some of the peptoids mimicking efficiently the effect of native SP-C, usually at larger proportions of peptoids than required for the natural protein.