Interactions of Bacterial Quorum Sensing Signals with Model Lipid Membranes: Influence of Acyl Tail Structure on Multiscale Response

Many
common bacteria use amphiphilic N-acyl-L-homoserine
lactones (AHLs) as signaling molecules to coordinate group behaviors
at high cell densities. Past studies demonstrate that AHLs can adsorb
to and promote the remodeling of lipid membranes in ways that could
underpin cell–cell or host–cell interactions. Here,
we report that changes in AHL acyl tail group length and oxidation
state (e.g., the presence or absence of a 3-oxo group) can lead to
differences in the interactions of eight naturally occurring AHLs
in solution and in contact with model lipid membranes. Our results
reveal that the presence of a 3-oxo group impacts remodeling when
AHLs are placed in contact with supported lipid bilayers (SLBs) of
the phospholipid 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC).
Whereas AHLs that have 3-oxo groups generally promote the formation
of microtubules, AHLs that lack 3-oxo groups generally form hemispherical
caps on the surfaces of SLBs. These results are interpreted in terms
of the time scales on which AHLs translocate across bilayers to relieve
asymmetrical bilayer stress. Quartz crystal microbalance with dissipation
measurements also reveal that 3-oxo AHLs associate with DOPC bilayers
to a greater extent than their non-3-oxo analogues. In contrast, we
observed no monotonic relationship between AHL tail length and bilayer
reformation. Finally, we observed that 3-oxo AHLs facilitate greater
transport or leakage of molecular cargo across the membranes of DOPC
vesicles relative to AHLs without 3-oxo groups, also suggesting increased
bilayer disruption and destabilization. These fundamental studies
hint at interactions and associated multiscale phenomena that may
inform current interpretations of the behaviors of AHLs in biological
contexts. These results could also provide guidance useful for the
design of new classes of synthetic materials (e.g., sensor elements
or drug delivery vehicles) that interact with or respond selectively
to communities of bacteria that use 3-oxo AHLs for cell–cell
communication.