Polyethylene glycols interact with membrane glycerophospholipids: is this part of their mechanism for hypothermic graft protection?

Abstract

Polyethylene glycol (PEG), a high-molecularweight colloid present in new organ preservation solutions, protects against cold ischemia injuries leading to better graft function of transplanted organs. This protective effect cannot be totally explained by immuno-camouflaging property or signaling-pathway modifications. Therefore, we sought for an alternative mechanism dependent on membrane fluidity. Using the Langmuir-Pockles technique, we show here that PEGs interacted with lipid monolayers of defined composition or constituted by a renal cell lipid extract. High-molecular-weight PEGs stabilized the lipid monolayer at low surface pressure. Paradoxically, at high surface pressure, PEGs destabilized the monolayers. Hypothermia reduced the destabilization of saturated monolayer whereas unsaturated monolayer remained unaffected. Modification of ionic strength and pH induced a stronger stabilizing effect of PEG 35,000 Da which could explain its reported higher effectiveness on cold-induced injuries during organ transplantation. This study sheds a new light on PEG protective effects during organ preservation different from all classical hypotheses.

Organ Preservation: Current Concepts and New Strategies for the Next Decade

“…However, PEGs are thought to stabilise the lipid monolayer in cell membranes, and the polymer has different effects on monolayers under low (fluid membrane) or high (condensed lipid bilayer) surface pressure that characterise compression of glycerophospholipids in the monolayer. Under condition of low surface pressure, PEGs stabilise membrane [69]. Part of this effect is associated with the dehydrating ability of PEGs to reduce the lipid molecular motion, which may cause denser packing of the lipids and a decrease in the membrane fluidity [70].…”

Antiviral Lipopeptide-Cell Membrane Interaction Is Influenced by PEG Linker Length

“…For VG-PEG24-Chol, a two-phase kinetics is observed ( Figure 1 C, section C1), in which a highly fast membrane insertion occurs for the first 20 s, followed by a moderate interaction for the rest of the assay. The perturbation of the lipid bilayer by PEG [ 41 ], together with the increased membrane absorption of longer polymers [ 42 ], may explain why VG-PEG24-Chol shows a better insertion rate than VG-PEG4-Chol.…”

Polyethylene glycol protects primary hepatocytes during supercooling preservation

“…Low molecular weight PEG (5kDa) is reported to accumulate in hepatocytes [13]. MWs of 400–20,000 were noted to activate JNK signaling which may be either protective or harmful [7] as well as interact with membrane glycerophospholipids [8], and the 35KDa PEG was noted to both protect against necrosis and enable membrane stabilization[8] in renal cells. The exact mechanisms remain to be elucidated, but our results demonstrate clear reduction in intracellular MDA levels as a direct result of 35kDa PEG.…”