Influence of acyl chain fluidity on the lipopolysaccharide-induced activation of complement

Lipopolysaccharides (LPSs. endotoxins) are the major amphiphilic constituen ts of the outer leaflet of the outer membrane of Gram-negative bacteria. Th ey are known to activate the complement cascade to form lytic membrane pore s. Here, we study the influence of the fluidity of the acyl chains of LPSs and lipid As on the formation of lytic pores. To this end, we have performe d electrical measurements on asymmetric planar endotoxin/phospholipid bilay ers as a reconstitution model of the outer membrane using two deep rough mu tant LPSs (from Escherichia coli strains WBB01 and WBB25) and two lipid As (from E. coli WBB25 and Rhodobacter sphaeroides). The two LPSs and the two lipid As each differ in their acylation pattern which is correlated with th e fluidity. The addition of human serum to the endotoxin side of the bilaye rs led to the formation of membrane pores, and pore formation correlated in each case with acyl chain fluidity. i.e. time required for the first lytic pore to be formed was shorter for the more fluid endotoxin. Furthermore, i n the case of LPSs, the activation rate was higher for the more fluid membr ane and the respective bacteria had a higher susceptibility to the growth i nhibitory action of serum.