Chain-Length-Dependent Partitioning of 1-Alkanols in Raft-Like Lipid Membranes

Although 1-alkanols are widely used as anesthetics and membrane-active agents, the molecular basis of their chain-length-dependent cutoff behavior remains unclear. Here, we perform extensive atomistic molecular dynamics simulations to investigate the partitioning of 1-alkanols with varying chain lengths in a raft-like lipid bilayer composed of dipalmitoylphosphatidylcholine (DPPC), dioleoylphosphatidylcholine (DOPC), and cholesterol (Chol), which exhibits coexistence of liquid-ordered ($l_o$) and liquid-disordered ($l_d$) domains. We observe pronounced lateral heterogeneity in alkanol distribution, membrane thickness, number density, and lateral pressure profiles across coexisting phases. A distinct cutoff chain length, $n_{cutoff}=12$, is identified: alkanols with $n