Molecular Dynamics simulations and Kelvin Probe Force microscopy to study of cholesterol-induced electrostatic nanodomains in complex lipid mixtures

TL;DR

This study combines molecular dynamics simulations with Kelvin Probe Force Microscopy to investigate how cholesterol influences the formation and electrical properties of nanodomains in lipid monolayers, revealing new insights into membrane function.

Contribution

It introduces an integrated experimental and computational approach to analyze cholesterol-induced electrostatic nanodomains in lipid monolayers, highlighting the molecular basis of electrical surface potential differences.

Findings

Cholesterol alters nanoscale domain formation affecting topography and electrical potential.

MD simulations qualitatively match experimental electrostatic potential differences.

Electrostatic potential differences between Lo and Ld phases suggest a new membrane function mechanism.

Abstract

The molecular arrangement of lipids and proteins within biomembranes and monolayers gives rise to complex film morphologies as well as regions of distinct electrical surface potential, topographical and electrostatic nanoscale domains. To probe these nanodomains in soft matter is a challenging task both experimentally and theoretically. This work addresses the effects of cholesterol, lipid composition, lipid charge, and lipid phase on the monolayer structure and the electrical surface potential distribution. Atomic Force Microscopy (AFM) was used to resolve topographical nanodomains and Kelvin Probe Force Microscopy (KPFM) to resolve electrical surface potential of these nanodomains in lipid monolayers. Model monolayers composed of dipalmitoylphosphatidylcholine (DPPC), 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC), 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), 1,2-dioleoyl-sn-glycero-3-[phospho-rac-(3-lysyl(1-glycerol))] (DOPG), sphingomyelin, and cholesterol were studied. It is shown that cholesterol changes nanoscale domain formation, affecting both topography and electrical surface potential. The molecular basis for differences in electrical surface potential was addressed with atomistic molecular dynamics (MD). MD simulations qualitatively match the experimental results, with 100s of mV difference in electrostatic potential between liquid-disordered bilayer (Ld, less cholesterol and lower chain order) and a liquid-ordered bilayer (Lo, more cholesterol and higher chain order). Importantly, the difference in electrostatic properties between Lo and Ld phases suggests a new mechanism by which membrane composition couples to membrane function.