A Model for Lipopolysaccharide-Membrane Interaction

Lipopolysaccharide (LPS), a major component of the outer membrane of gram-negative bacteria, is a complex macromolecule both structurally and functionally (1). It induces metabolic and cellular changes mediating host defenses as well as pathogenesis (2,3). Unlike many macromolecules of biological importance, there is little data on the nature of the target cell structure with which LPS interacts. The structure of LPS and the importance of lipid A in biological activities has led to the assmuption that LPS interacts hydrophobically with the plasma membrane of target cells by edge attachment of LPS bilayers (4). However, since the prototype monomer of LPS is an amphiphile, LPS exists as bilayer or vesicular aggregates in solution, arrangements without edges (5). In addition, there is scant direct evidence in the literature that LPS interaction with cell membranes is hydrophobic. One recent paper examined fluorescence anisotropy of macrophages exposed to LPS using DPH; however, the time and temperature did not preclude the possibility that the measurements made reflected changes in internal membranes due to physiological activation by LPS (6). A few studies have demonstrated an interaction between LPS and phospholipid monolayer or bilayer films as detected by changes in surface pressure and surface potential (7,8).