The Flow of Proteins and Idealised Pores within the Membranes of Gram-Negative Bacteria

Abstract

Gram-negative bacteria are protected by a complex cell envelope. Understanding the structure-dynamics-function relationships within the Gram-negative cell envelope is key to the ongoing fight against the emergence of bacterial resistance to antibiotics. The Gram–negative cell envelope consists of two membranes, separated by a cell wall. The membranes contain a variety of proteins, which make up to 25% of the bilayer surface area. Lipid-protein interactions are significant in determining the function and organisation of membrane proteins, through macroscopic bilayer properties or specific protein-lipid interactions. Computational and experimental studies have revealed that proteins and lipids diffuse together as complexes, which have dynamical properties that differ from the properties of unbound lipids. However it is unclear how much the size, shape and biochemistry of the macromolecules contribute to these altered dynamics. Here we present the results of coarse–grained simulations that uncover the structural and dynamic effects of a series of outer membrane proteins (OMPs) and functionlised carbon nanotubes (CNTs) on biologically relevant models of the inner and outer membranes of E. coli. Investigating such a range of nanopores provides an insight into the effects the chemistry and topology of an embedded protein have on the local membrane environment. We show that the flow of molecules in the outer membrane is asymmetrical, reflecting the lipid composition of this membrane. Flow of proteins and lipids are highly correlated in the outer leaflet and much less so in the inner leaflet of the membrane.