Experimental and Monte Carlo Simulation Studies of the Thermodynamics of Polyethyleneglycol Chains Grafted to Lipid Bilayers

Abstract

Experimental measurements of the affinity of binding of fluorescent acylated polyethyleneglycol (PEG) conjugates to bilayers containing varying levels of phosphatidylethanolamine-PEGs (PE-PEGs) have been combined with Monte Carlo simulations to investigate the properties of the polymer chains at a PEG-grafted lipid interface. The affinity of binding of such conjugates to large unilamellar phosphatidylcholine/phosphatidylethanolamine (9:1) vesicles decreases 27-fold as the size of the coupled PEG chain increases from 1 to 114 monomer units. Incorporation of increasing amounts of PE-PEG2000 or PE-PEG5000 into the vesicles progressively reduces the affinity of binding of acylpeptide-PEG2000 or -PEG5000 conjugates. Monte Carlo simulations of surfaces with grafted PEG chains revealed no significant dependence of several characteristic properties of the polymer chains, including the average internal energy per polymer and the radii of gyration, on the grafting density in the range examined experimentally. The average conformation of a surface-grafted PEG2000 or PEG5000 chain was calculated to be fairly extended even at low grafting densities, and the projected cross-sectional areas of the grafted PEG chains are considerably smaller than those predicted on the basis of the estimated Flory radius. The experimental variation of the binding affinity of acylated conjugates for bilayers containing varying mole fractions of PE-PEG2000 or -PEG5000 is well explained by expressions treating the surface-grafted PEG polymers either as a van der Waals gas or as a system of rigid discs described by scaled particle theory. From the combined results of our experimental and simulation studies we conclude that the grafted PEG chains exist in a "mushroom" regime throughout the range of polymer densities examined experimentally and that the diminished affinity of binding of acylated-PEG conjugates to bilayers containing PE-PEGs results from occlusion of the surface area accessible for conjugate binding by the mobile PE-PEG polymer chains.

A New Lipid-Based Nano Formulation of Vinorelbine

“…In fact, this explanation supports the decrease in size of micelle after large number of drug molecules are loaded in SSM interface, causing PEG to fold more, making the PEG layer thinner (Fig. 10) (50). We have observed similar phenomena when we included water insoluble lipid, phosphatidylcholine, into PEGylated lipid micelles (21).…”

PEG conjugation moderately protects adeno-associated viral vectors against antibody neutralization

“…The Flory radius R F of free polymer in solution can be estimated by R F ¼ C * N 3/5 (Flory and Fisk, 1966), where C is the effective ''bond'' length and N is the statistical number of monomers. For PEG, the constant C was found to be 3.5 Å (Rex et al, 1998), and for MW 2000 PEG the R F can therefore be estimated as approximately 39 Å . The size of a polymer near a surface may be approximated as the Flory radius (Szleifer, 1996).…”

“…The size of a polymer near a surface may be approximated as the Flory radius (Szleifer, 1996). More recent calculations based on de Gennes theory and molecular simulation have found that for PEG chains grafted onto lipid bilayers, the cross-sectional surface area ''coverage'' is actually smaller (Kenworthy et al, 1995;Kuhl et al, 1994;Rex et al, 1998). Specifically, Rex et al found that the diameter of the cross-sectional coverage for PEG 2000 chains to be only approximately 18 Å , a more conservative number that we chose for our analysis.…”

Adhesion of Polymer Vesicles

“…This surface is analogous to a fluid brush of polymer chains that are anchored in the hydrophobic membrane [2]. The scaling of the fundamental physical properties of fluid polymer brushes has been addressed through self-consistent mean field theories [3][4][5][6], Monte Carlo simulations [7,8], and density functional theory [9]. We report the results of adhesion and modulus measurements along with a model based on the physical properties and structure of the adhesive vesicle surface.…”