Striated domains in biological model membranes AFM and computer simulation studies of lipid bilayers and the model peptide WALP

Abstract

Lateral assembly in biological membranes is important as many proteins are switched from a non-active to an active state by membrane-mediated effects. Here, self-assembly in biological, gel-phase model membranes with the model peptide WALP was studied. Domains with a striated appearance are formed in these systems, which consists of lines of the single, alpha-helical WALP alternating with lines with a width of 4 - 5 lipids with a reduced tilt angle. Results from Atomic Force Microscopy (AFM) show that the lipid environment determines the propensity of the system to form a striated phase when the phase or type (i.e. chemical nature) of the lipids in the bilayer varies. Both the presence of a tightly-packed bilayer in the solid phase and of a non-zero tilt angle of the lipid’s acyl chains are essential. No striated domains are formed when the tilted DPPC lipids are replaced by non-tilted DPPE lipids, or when the bilayer is not tightly packed. This latter occurs in bilayers of DPPC in the fluid phase or of PC lipids with an unsaturated cis-bond in their acyl chain in the solid phase. The extent of hydrophobic mismatch between peptide and lipid bilayer, however, does not influence the striated phase under different negative mismatch conditions. Computer simulations (Dissipative Particle Dynamics or DPD technique) give insight on a molecular scale and corroborate the findings of AFM. Coarse-grained models for water and the lipids and peptides are used, where a number of atoms are grouped together as larger beads that mimic the polar and non-polar groups of the molecules. Inclusion of a row of rigid WALP molecules leads to non-monotonously decaying profiles of the chain disorder, tilt angle and shape and thickness of a DPPC bilayer as function of the distance to the peptide. The well-defined spacing in the striated phase is believed to originate from overlap of the perturbed regions from two opposing rows of WALP. The conformational perturbation of a non-tilted DPPE bilayer and a fluid DPPC bilayer are smaller and do not emanate over such large distances. No overlap occurs in these systems, in agreement with the absence of a striated phase in the experimental systems for DPPE and in the fluid phase.