Divergent Responses of Branched and Straight-Chain Lipid Membranes to Butanol Stress Revealed by Molecular Dynamics Simulation

Abstract

Membrane integrity under chemical stress is critical to cellular survival and industrial microbial bioproduct formation, yet the molecular determinants that govern bilayer resilience remain incompletely understood. Here, we use all-atom molecular dynamics simulation to compare the biophysical responses to increasing concentrations of 1-butanol membranes comprising unbranched, saturated (1,2-dipalmitoyl-sn-glycero-3-phosphocholine, DPPC) and branched, saturated (1-anteiso-palmitoyl-2-palmitoyl-sn-glycero-3-phosphocholine, APPC) lipids. These two lipids differ by a single methyl group attached to the APPC system. In the absence of butanol, both membranes exhibit well-ordered architectures consistent with experimental benchmarks; however, under increasing solvent stress, their behaviors diverge markedly. DPPC membranes display gradual thinning, modest area per lipid expansion, and sustained acyl-chain order, resulting in only moderate declines in bending rigidity and lateral mobility. In contrast, APPC bilayers exhibit accelerated thinning, pronounced lateral expansion, and significant loss of chain order, culminating in enhanced interleaflet overlap and a sharp decline in bending modulus, reflecting a fundamental breakdown of bilayer symmetry and mechanical resistance. Together, our findings reveal how lipid tail architecture modulates membrane vulnerability to organic solvents and suggest that branching, while potentially beneficial under thermal stress, renders membranes more susceptible to solvent-induced collapse.