Structural Properties of Inverted Hexagonal Phase: A Hybrid Computational and Experimental Approach

Area of Science:

• Physical chemistry
• Biophysics
• Computational modeling

Background:

• Inverted hexagonal (HII) lipid phases are crucial in nanomedicine and biological systems.
• Understanding HII phase behavior requires detailed structural and dynamic information.

Purpose of the Study:

• To investigate the structural parameters of HII phases composed of dioleoylphosphatidylethanolamine (DOPE) and palmitoyloleoylphosphatidylethanolamine (POPE) using molecular dynamics (MD) simulations.
• To determine the effects of hydration level and temperature on HII structural parameters, including deuterium order parameters and water core radius.
• To compare the HII structures formed by DOPE and POPE to understand the influence of acyl chain unsaturation.

Main Methods:

• Molecular dynamics (MD) simulations of DOPE and POPE lipid systems at various hydration levels and temperatures.
• Deuterium nuclear magnetic resonance (2H NMR) and small-angle X-ray scattering (SAXS) experiments for validation.
• Estimation of maximum hydration levels for DOPE and POPE HII lattices.

Main Results:

• MD simulation results showed excellent agreement with experimental data (2H NMR, SAXS).
• Dehydration decreased the water core radius; increased hydration slightly increased lipid acyl chain order parameters.
• Increased temperature decreased acyl chain order parameters, maximum hydration, water core radius, and lattice plane distances.

Conclusions:

• MD simulations provide a reliable method for predicting HII phase behavior and structural parameters.
• A protocol for constructing computational HII systems that accurately represent experimental systems was proposed.
• The findings contribute to the development and validation of force field parameters for lipid simulations in nanomedicine.