Environmental Stability of Alkyl Phosphate- and Sulfate-Containing Membranes as Early Cell Models

Abstract The ability of simple amphiphiles to assemble into stable membranes is central to understanding how protocells may have formed on early Earth. In this work, we examine how small structural differences, specifically hydrocarbon chain length and headgroup identity, influence membrane formation, stability, and permeability in mixed amphiphile systems exposed to diverse conditions to understand the role of the environment in protocell evolution. Using automated sample preparation and confocal microscopy, we characterized eight compositions containing decyl sulfate (DS), dodecyl sulfate (DDS), or dodecyl phosphate (DDP) across a range of pH values in ultrapure water, sea salt, or sea salt mixed with a complex prebiotic organic solution. Longer-chain and phosphate-containing amphiphiles formed more vesicles, particularly at low pH and high ionic strength. DS exhibited consistently low and environment-insensitive critical vesicle concentrations (CVCs), whereas DDP displayed the highest sensitivity to alkaline conditions. DDP-containing vesicles were the least permeable, highlighting the lipid packing influence of the phosphate headgroup. Together, these findings show that small modifications in amphiphile composition strongly affect membrane properties across early Earth-like environments, demonstrating the role of anionic surfactants in protocell emergence.