Interactions of surfactin with ether-linked and ester-linked lipid membranes: A molecular dynamics simulation study

Surfactin is a biosurfactant with diverse applications, including antibacterial and antiviral activity, primarily attributed to its ability to destabilize lipid bilayers. Previous studies have focused on ester-linked lipids, where destabilization has been associated with reduced hydration around ester carbonyl groups. Here, we employ molecular dynamics simulations to investigate surfactin's effect on ether-linked lipids, which lack carbonyl groups and are characteristic of archaeal membranes known for their exceptional stability. We compared tetraether lipids and a diether lipid along with its ester-linked analogue. Among the ether-linked systems, the macrocyclic tetraether lipid showed the strongest response to surfactin insertion, whereas the diether lipid was minimally perturbed. By contrast, the ester-linked analogue underwent significant compression and increased water penetration into the bilayer. These findings reveal that membrane susceptibility to surfactin depends critically on both linkage chemistry and lipid architecture, with ester linkages and tetraether backbones promoting destabilization to a greater extent than diether systems.