Effects of block copolymer's architecture on its association with lipid membranes: experiments and simulations.
Triblock copolymers of the form poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (PEO-PPO-PEO) have been shown to effectively interact with and restore activity of damaged cell membranes. To better understand the interaction between these polymers and cell membranes, we have modeled the outer leaflet of a cell membrane with a lipid monolayer spread at the air-water interface and injected poloxamers of varying architectures into the subphase beneath the monolayer. Subsequent interactions of the polymer with the monolayer upon compression were monitored with concurrent Langmuir isotherm and fluorescence microscopy measurements. Monte Carlo simulations were run in parallel using a coarse-grained model to capture interactions between lipids and poloxamers. Changing the ratio of the PEO to PPO block lengths (NPEO:NPPO) affects the equilibrium spreading pressure of the polymer. Poloxamers with a relatively longer central hydrophobic block are less soluble, resulting in more polymer adsorbed to the interface and therefore a higher equilibrium spreading pressure. Simulation results show that changing the poloxamer structure effectively affects its solubility. This is also reflected in the degree of lipid corralling as poloxamers with a higher chemical potential (and resulting higher equilibrium spreading pressure) cause the neighboring lipid domains to be more ordered. Upon lateral compression of the monolayers, the polymer is expelled from the film beyond a certain squeeze-out pressure. A poloxamer with a higher NPEO:NPPO ratio (with either NPEO or NPPO held constant in each series) has a lower squeeze-out pressure. Likewise when the total size of the polymer is varied with a constant hydrophilic:hydrophobic ratio, smaller poloxamers are squeezed out at a lower pressure. Our simulation results capture the trends of our experimental observations, both indicating how the interactions between lipids and poloxamers can be tuned by the polymer architecture.
Frey
Shelli L
SL
Department of Chemistry, Institute for Biophysical Dynamics and James Franck Institute, The University of Chicago, Chicago, Illinois 60637, USA.
Zhang
Dongsheng
D
Carignano
Marcelo A
MA
Szleifer
Igal
I
Lee
Ka Yee C
KY
D015060:1,2-Dipalmitoylphosphatidylcholine / Q000737:chemistry; D002462:Cell Membrane / Q000378:metabolism; D002627:Chemistry, Physical / Q000379:methods; D003198:Computer Simulation; D008055:Lipids / Q000737:chemistry*; D008823:Micelles; D008856:Microscopy, Fluorescence / Q000379:methods; D009010:Monte Carlo Method; D020442:Poloxamer / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D011108:Polymers / Q000737:chemistry*; D011126:Polypropylenes / Q000737:chemistry; D011312:Pressure; D012995:Solubility; D014867:Water / Q000737:chemistry
D008055:Lipids; D008823:Micelles; D011108:Polymers; D011126:Polypropylenes; D014867:Water; D020442:Poloxamer; D015060:1,2-Dipalmitoylphosphatidylcholine; D011092:Polyethylene Glycols