Mixing Behavior of a Poly(ethylene glycol)-Grafted Phospholipid in Monolayers at the Air/Water Interface

Abstract

Mixed phospholipid monolayers hosting a poly(ethylene glycol) (PEG)-grafted distearoylphosphatidylethanolamine with a PEG molecular weight of 5000 (DSPE-PEG5000) spread at the air/water interface were used as model systems to study the effect of PEG-phospholipids on the lateral structure of PEG-grafted membrane-mimetic surfaces. DSPE-PEG5000 has been found to mix readily with distearoylphosphoethanolamine-succinyl (DSPE-succynil), a phospholipid whose structure resembles closely that of the phospholipid part of the DSPE-PEG5000 molecule. However, properties of mixed monolayers such as morphology and stability varied significantly with DSPE-PEG5000 content. In particular, our surface pressure, epifluorescence microscopy (EFM), and Brewster angle microscopy (BAM) studies have shown that mixtures containing 1-9 mol % of DSPE-PEG5000 form stable condensed monolayers with no sign of microscopic phase separation at surface pressures above approximately 25 mN/m. Yet, at 1 mol % of DSPE-PEG5000 in mixed monolayers, the two components have been found to behave nearly immiscibly at surface pressures below approximately 25 mN/m. For monolayers containing 18-75 mol % of DSPE-PEG5000, a high-pressure transition has been observed in the low-compressibility region of their isotherms, which has been identified on the basis of continuous BAM imaging of monolayer morphology, as reminiscent of the collapse nucleation in a pure DSPE-PEG5000 monolayer. Thus, the comparative analysis of our surface pressure, EFM, and BAM data has revealed that there exists a rather narrow range of mixture compositions with DSPE-PEG5000 content between 3 and 9 mol %, where somewhat homogeneous distribution of DSPE-PEG5000 molecules and high pressure stability can be achieved. This finding can be useful to "navigating" through possible mixture compositions while developing guidelines to the rational design of membrane-mimetic surfaces with highly controlled bio-nonfouling properties.

Quantification of PEG40St squeeze out from DSPC/PEG40St monolayers at higher molar ratios

“…< A 2 > . However, the true mean molecular area could not be accurately estimated for each component during the measurements due to attractive-repulsive forces between the component molecules and their complexations [30][31][32][33]. The mixture could be considered "ideal" if the component molecules have no irregular packing attachments, no complex formations, and form a phase separation in the monolayer [6,30].…”

“…Different regions of the Langmuir isotherm can give information on the phase behavior of the molecules for each component. It was shown that more ordered and rigid monolayers collapse at relatively higher surface pressures, usually by fracturing, followed by loss of materials to the air side with the formation of multilayered aggregates, or to the sub phase with budding or vesicle formation [25,29,31,34]. When a binary mixture of components having two different collapse pressures were compressed, at least two plateaus will exhibit, one is at the lower collapse pressure for the expanded phase and the other is at the higher collapse pressure for the more rigid component [6,[35][36][37][38].…”

Effect of Saline on Transitions in Poly(ethylene glycol)-Grafted Succinyl-Phosphoethanolamine Monolayers Bearing C16Aliphatic Chains

“…Studies performed in saline-containing aqueous solutions have reported that PEG hydration and conformational behavior can be affected by saline in a way not easily predictable by existing theories. − Moreover, interactions with saline may influence the miscibility and phase of constituents of PEG-grafted lipid surfaces . Although much has been learned about the self-assembly of lipids and PEG−lipid conjugates, ,− the effect of saline on their miscibility, phase, and conformational behavior at surfaces and interfaces has not yet been systematically studied.…”

“…Among various model systems, PEG−lipid monolayers at the air/water interface have proven to provide ideal models of PEG-grafted lipid surfaces. ,− The advantage of these monolayers as model systems is that they allow the precise control of parameters such as lateral (surface) pressure and area per lipid molecule, which is not possible with bilayers and liposomes/vesicles. Wide range variations of PEG grafting density can be easily simulated in a well-controlled manner by the monolayer compression.…”

“…Wide range variations of PEG grafting density can be easily simulated in a well-controlled manner by the monolayer compression. Moreover, continuous observation of monolayer morphology upon compression with imaging techniques offers a unique opportunity to monitor the phase behavior of constituents of PEG-grafted lipid surfaces and how it changes depending on various factors. ,,, Hence, the study of PEG−lipid monolayers provides a basis for understanding the phase and conformational behavior of any PEG-grafted lipid surface. To date, significant attention has been given to the conformational transitions in PEG chains grafted on monolayers at the air/water interface. ,− By contrast, only a few studies have attempted to gain insight into the miscibility, phase, and conformational behavior of PEG-grafted lipid monolayers spread on aqueous subphases of biological relevance; in particular, phosphate buffered saline (PBS). , …”