Membrane Sealing by Polymers

Abstract

An intact cell membrane serves as a barrier, controlling the traffic of materials going into and out of the cell. When the integrity of the membrane is compromised, its transport barrier function is also disrupted, leaving the cell vulnerable to necrosis. It has been shown that triblock copolymer surfactants can help seal structurally damaged membranes, arresting the leakage of intracellular materials. Using model lipid monolayers along with concurrent Langmuir isotherm and fluorescence microscopy measurements as well as surface X-ray scattering techniques, the nature of the interaction between lipids and a particular family of triblock copolymers in the form poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) is examined. The polymer is found to selectively insert into membranes where the lipid packing density is below that of an intact cell membrane, thus localizing its sealing effect on damaged portions of the membrane. The inserted polymer is "squeezed out" of the lipid film when the lipid packing density is increased, suggesting a mechanism for the cell to be rid of the polymer when the membrane integrity is restored.

Poloxamer 188 reduces the contraction-induced force decline in lumbrical muscles from mdx mice

“…Previous studies have established P188 as a membranepatching polymer that interacts directly with monolayers (33) and disrupted membranes (22). P188 is effective in stabilizing membranes and enhances the recovery of a variety of cell types from an array of injury-inducing protocols (7,20,25,34).…”

“…P188 is a 8.4-kDa amphiphilic polymer that localizes into lipid monolayers (33) and damaged portions of membranes (22). When applied to injured cells, P188 repairs disrupted membranes and enhances the recovery of skeletal muscle (20), fibroblasts (25), cardiac myocytes (34), and the spinal cord (7) from a variety of injury-inducing protocols.…”

Novel mucus-penetrating liposomes as a potential oral drug delivery system: preparation, in vitro characterization, and enhanced cellular uptake

“…19 It is widely accepted that Pluronic polymers can stabilize and seal damaged lipid bilayer membranes. [34][35][36] Considering that the PF127 is adsorbed on the outer leaflet of the bilayer (PF127-adsorbed liposomes), it may be easily lost by simple diffusion. It might then interact with the cell membrane, altering the membrane fluidity and membrane interaction, and finally stabilizing the membrane structure.…”

Interaction of poloxamine block copolymers with lipid membranes: Role of copolymer structure and membrane cholesterol content

“…For example, Tetronic 1107 has been shown to protect erythrocytes and lymphocytes from ionizing radiation [22]. For membrane sealing applications, the copolymers have been tested at concentrations (0.1-1.0 mM; roughly 1-10 mg/mL) below, but close to, the CMC in order to maximize the concentration of unimers [9]. Regarding structure-activity relationships, poloxamer varieties with short PPO block (e.g., Pluronic F68) have been shown to insert the PPO block in the bilayer as a loop with the two PEO end blocks extending laterally onto the phospholipid heads at the same side of the membrane; namely, the PPO chain length does not allow for membrane spanning, but the PEO chains can effectively seal defects on the membrane.…”

“…Pluronic P85 was chosen due to its reported capability to insert into the lipid bilayer and alter diverse cell pathways to inhibit P-glycoprotein efflux pumps [1]. Although poloxamine-lipid monolayer systems have not been evaluated before, it has been pointed out that poloxamines might be more effective as membrane sealant than poloxamers due to their bulkier hydrophobic center [9]. Additionally, the protective effect of the block copolymers on erythrocyte hemolysis was recorded.…”