Lipid corralling and poloxamer squeeze-out in membranes

COLL 424

Guohui Wu1, Jaroslaw Majewski2, Canay Ege1, Markus Weygand3, Kristian Kjaer3, and Ka Yee C. Lee1. (1) Department of Chemistry, The Institute for Biophysical Dynamics & The James Franck Institute, The University of Chicago, 5735S. Ellis Ave., Chicago, IL 60637, (2) LANSCE-12, Los Alamos National Laboratory, MS H805, Los Alamos, NM 87544, (3) Condensed Matter Physics and Chemistry Department, Risø National Laboratory, Denmark, Roskilde, DK-4000, Denmark
Victims of electrical trauma suffer extensive loss of structural integrity of cell membranes. Stable structural defects – "pores" in the range of 0.1 mm – have been demonstrated in electroporated cell membranes. Poloxamer 188, a triblock copolymer of the form poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) is known to help seal electroporated cell membranes, arresting the leakage of intracellular materials of the damaged cell. Using a monolayer to mimic the outer leaflet of the cell membrane, we have examined the interaction between the poloxamer and dipalmitoylphosphatidylcholine or dipalmitoylphosphatidylglycerol monolayers. With synchrotron x-ray reflectivity and grazing-incidence x-ray diffraction, both the out-of-plane and in-plane structures of mixed phopholipid-poloxamer 188 monolayers were investigated at the air-water interface. P188 selectively inserts into low lipid-density regions of the membrane and "corrals" lipid molecules to pack tightly, leading to unexpected Bragg peaks at low nominal lipid density and inducing the film to separate into P188-rich and -poor phases. At tighter lipid packing, the once inserted P188 is squeezed out, providing a route for the poloxamer to gracefully exit when the membrane integrity is restored.