BPS2026 – Amphiphilic co-solvents alter lateral membrane organization

Solvent toxicity sets the upper limit of biomass fermentation titer and yield. Solvent molecules produced during biomass fermentation, such as ethanol and butanol, induce stress as these amphiphilic molecules partition into biomembrane, leading to membrane thinning, destabilization, and ultimately cell death. However, this stress induced by amphiphilic co-solvents does not fully account for their effects on lateral membrane organization. In this study, we utilized small angle neutron scattering and molecular dynamics simulations to investigate the toxic effects of n-butanol on both transverse and lateral membrane structure. Our scattering experiments demonstrated the extent of n-butanol partitioning, solvent-induced membrane thinning, and solvent-induced changes in line tension. Simulations provided atomic-level details of the transverse and lateral membrane structure, as well as mechanical properties of membrane in presence of co-solvent. Together, our results present a mechanism by which membrane domain coalesced into fewer, larger domains to minimize the ratio of domain boundary length to domain area. This alteration of membrane domains in the presence of co-solvent is an unrecognized mode of membrane-solvent-associated cellular stress and may point to a new direction for improving microbial solvent tolerance.