Concentration-Dependent Membrane Destabilization in DPPC Bilayers: Distinct Insertion Mechanisms and Stress Redistribution by Chloroform and Alkanols

TL;DR

This study uses molecular dynamics simulations to explore how different solutes and their concentrations affect membrane stability, revealing distinct insertion mechanisms and stress redistribution patterns in DPPC bilayers.

Contribution

It provides detailed insights into how chloroform and alkanols influence membrane destabilization through their unique insertion behaviors and concentration-dependent effects.

Findings

Chloroform causes significant membrane thinning and large fluctuations.

Ethanol shows intermediate insertion and effects.

Octanol preserves thickness but increases fluctuations and interdigitation.

Abstract

How do solute concentration and molecular chemistry govern the transition from membrane saturation to destabilization? We address this using microsecond-scale molecular dynamics simulations of dipalmitoylphosphatidylcholine (DPPC) bilayers with chloroform (CHCl$_3$) and a homologous series of alkanols (methanol, ethanol, octanol) over $0-50\%$ concentrations. Although complete membrane melting is not observed within $1000\, ns$, all systems exhibit clear precursors of destabilization, including enhanced thickness fluctuations, reduced lipid order, and mechanical softening. Chloroform induces pronounced thinning and large fluctuations, consistent with deep, transient insertion. Methanol perturbs primarily the headgroup region, while ethanol shows intermediate behavior with partial insertion. Octanol preserves bilayer thickness at high concentrations due to lipid-like insertion but significantly increases fluctuations and interdigitation. Across all systems, increasing concentration decreases the area compressibility modulus and deuterium order parameter, accompanied by smoothing of lateral pressure profiles, indicating stress redistribution. Free energy analysis reveals increased membrane partitioning and reduced translocation barriers with concentration, strongest for octanol and weakest for methanol. These results demonstrate that membrane destabilization is governed by the interplay of insertion depth, interfacial crowding, and lipid packing disruption.