2 research outputs found
Interactions of polyethylenimines with zwitterionic and anionic lipid membranes
Interactions between
polyethylenimines (PEIs) and phospholipid
membranes are of fundamental importance for various biophysical applications
of these polymers such as gene delivery. Despite investigations into
the nature of these interactions, their molecular basis remains poorly
understood. In this article, we combined experimental methods and
atomistic molecular dynamics (MD) simulations to obtain comprehensive
insight into the effect of linear and branched PEIs on zwitterionic
and anionic bilayers used as simple models of mammalian cellular membranes.
Our results show that PEIs adsorb only partially on the surface of
zwitterionic membranes by forming hydrogen bonds to the lipid headgroups,
whereas a large part of the polymer chains dangles freely in the aqueous
phase. In contrast, PEIs readily adhere to and insert into the anionic
membrane. The attraction of the polymer chains to the membrane is
due to electrostatic interactions as well as hydrogen bonding between
the amine groups of PEI and the phosphate groups of lipids. These
interactions were found to induce a substantial reorganization of
the bilayer in the polymer vicinity due to the reorientation of lipid
molecules. The lipid headgroups were pulled toward the center of the
membrane, which can facilitate transmembrane translocations of anionic
lipids. Furthermore, the PEI鈥搇ipid interactions affect the
stability of liposomal dispersions, but we did not see any evidence
of disruption of the vesicular structures into small fragments at
polymer concentrations typically used in gene therapy. Our results
provide a detailed molecular-level description of the lipid organization
in the membrane in the presence of polycations that can be useful
in understanding their mechanisms of in vitro and in vivo cytotoxicity