2025 AIChE Annual Meeting

(698d) Understanding Formation of Cholesterol Clusters in a Biomimetic Solvent Using Mesoscale Molecular Simulations

Authors

Hasan Zerze, Lehigh University
Peter G. Vekilov, University of Houston
Jeffrey Rimer, University of Houston
Gül Zerze, Princeton University
Cholesterol plays a vital role in maintaining the structure and function of cell membranes. However, elevated cholesterol levels in the bloodstream can trigger the formation of cholesterol crystals, contributing to cardiovascular diseases. Recent experimental studies, using alcohol-water mixtures as biomimetic solvents, have revealed that stable cholesterol clusters form prior to crystal nucleation. Despite these advances, the molecular mechanisms underlying cholesterol cluster formation at the mesoscale remain poorly understood.

In this study, we employed molecular dynamics simulations with a Lennard-Jones-based mesoscale potential to model the behavior of a ternary ethanol-water-cholesterol system. Experimental data from solubility experiments and dimerization free energies from atomistic simulations were used to validate the solute-solvent model. Our simulations captured the formation of cholesterol dimers, which act as precursors to the growth of larger clusters and thereby pathological crystals. We further analyzed the orientation and interactions of cholesterol molecules within these dimers and clusters, providing insights into their self-assembly. This work lays the foundation for future studies on larger systems, ultimately advancing our understanding of cluster growth and the conditions leading to crystal nucleation.