Robustness of heteroaggregates involving hydrophobic cholesterol and its mimetics

Exploring the self and cross aggregation affinity of cholesterol (CHL) and some of its lookalikes, e.g. , cholesteryl hemisuccinate (CHM), campesterol (CAM) and arjunic acid (ARJ), provides crucial understanding towards the influence of weak forces in inducing mixed micellization through heteroaggregation. Strongly hydrophobic CHL, with a benchmark inclination towards aggregation, often forms detrimental plaques in crucial human organs that are fairly difficult to disintegrate. Traditionally known anti-dyslipidemic agents like CAM and ARJ are known to interact strongly with CHL in the gut when ingested. They further form mixed micelles along with the bile components and interfere with the CHL absorption across the epithelial cell layer of the intestine. Some invariant questions like how robust are the heteroaggregates formed between these mimetics and CHL are very important to appreciate the efficacy of such anti-dyslipidemic agents. In this work using molecular dynamics simulations and varied structural analysis, we characterize the heteroaggregates. Simulations indicate that CHL-CHM mixed assemblies are comparatively bigger and significantly stabilized by strong electrostatic and favourable vdW forces. Small and diffused CHL-ARJ aggregates are observed in our simulations with a not so favourable energetics, indicating a possible attenuation pathway of CHL aggregation in the presence of ARJ. Heteroaggregation affinity of cholesterol and its mimetics like cholesteryl hemisuccinate, campesterol and arjunic acid provides crucial understanding of the role of weak forces in inducing mixed micellization.