Differential effects of lipid bilayers on αPSM peptide functional amyloid formation

Phenol-soluble modulins (PSM) are key virulence factors of <i>S. aureus </i>and they comprise the structural scaffold of biofilm as they self-assemble into functional amyloids. They have been shown to interact with cell membranes as they display toxicity towards human cells through cell lysis with αPSM3 being the most cytotoxic. Besides causing cell lysis in mammalian cells PSMs have also been shown to interact with bacterial cell membranes through antimicrobial effects. Here, we present a study on the effects of lipid bilayers on the aggregation mechanism of αPSM using chemical kinetics to study the effects of lipid vesicles on the aggregation kinetics and using CD, FTIR and TEM to investigate the corresponding secondary structure of the aggregates. We find that the effects of lipid bilayers on αPSM aggregation are not homogeneous between lipid type and αPSM peptides although none of the lipids caused changes in the dominating aggregation mechanism. In the case of αPSM3 all types of lipids slowed down aggregation to a varying degree with DOPC having the most pronounced effect. For αPSM1 lipids have opposite effects where DOPC decelerated aggregation and LPS accelerated the aggregation while DOPG had no effect. For αPSM4 both DOPG and LPS accelerated the aggregation but only at high concentration while DOPC showed no effect. None of the lipids were capable of inducing aggregation of αPSM2. Our data reveal a complex interaction pattern between PSMs peptides and lipid bilayers that causes changes in the aggregation kinetics by affecting different kinetic parameters along with only subtle changes in morphology.