Adsorption of Plasma Proteins onto PEGylated Lipid Bilayers: The Effect of PEG Size and Grafting Density

被引:82
作者
Lee, Hwankyu [1 ]
Larson, Ronald G. [2 ,3 ]
机构
[1] Dankook Univ, Dept Chem Engn, Yongin 448701, South Korea
[2] Univ Michigan, Dept Chem Engn Biomed Engn Mech Engn & Macromol S, Ann Arbor, MI 48109 USA
[3] Univ Michigan, Engn Program, Ann Arbor, MI 48109 USA
基金
新加坡国家研究基金会;
关键词
COARSE-GRAINED MODEL; NONVIRAL GENE DELIVERY; ATTACHED POLY(ETHYLENE GLYCOL); LINEAR CONSTRAINT SOLVER; HUMAN SERUM-ALBUMIN; MOLECULAR-DYNAMICS; POLYETHYLENE OXIDE; CHAIN-LENGTH; SURFACE INTERACTIONS; CELL-INTERACTIONS;
D O I
10.1021/acs.biomac.6b00146
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Lipid bilayers grafted with polyethylene glycol (PEG) of different sizes (M-w = 750, 2000, and 5000) and grafting densities (1.6-25 mol % of PEGylated lipid in dipalmitoylphosphatidylcholine (DPPC) lipid molecules) were simulated with human serum albumin (HSA) using coarse grained force fields. At low enough grafting density, the PEG has a conformation similar to that of an isolated chain in water, and its Flory radius R-F is smaller than the distance between the grafting points (d), which is the so-called "mushroom" regime. In contrast, densely grafted PEG chains (R-F > d) extend like brushes, with brush layer thickness given by the Alexander-de Gennes theory. A nearly spherical HSA added to this simulation migrates to the bilayer surface because of the charge interactions between anion residues of HSA and cationic cholines of DPPC, but this HSA-bilayer binding can be sterically suppressed by the PEG chains to an extent that depends on the PEG size and grafting density. In particular, regardless of the extent of the coverage of the PEG on the bilayer, the binding between HSAs and bilayers is suppressed by the PEG layer in a brush but not in a mushroom, indicating that the attractive force between proteins and bilayers can overcome the steric effect of the PEG layer in the mushroom state or in the transition region from mushroom to brush. This helps explain and clarify experiments that show much less adsorption of plasma proteins onto the particle or membrane surface when PEGs are in the brush rather than in the mushroom state.
引用
收藏
页码:1757 / 1765
页数:9
相关论文
共 82 条
[1]   LIPOSOMES CONTAINING SYNTHETIC LIPID DERIVATIVES OF POLY(ETHYLENE GLYCOL) SHOW PROLONGED CIRCULATION HALF-LIVES INVIVO [J].
ALLEN, TM ;
HANSEN, C ;
MARTIN, F ;
REDEMANN, C ;
YAUYOUNG, A .
BIOCHIMICA ET BIOPHYSICA ACTA, 1991, 1066 (01) :29-36
[2]  
[Anonymous], 1961, Physical Chemistry of Macromolecules
[3]   Interaction of human serum albumin with membranes containing polymer-grafted lipids: spin-label ESR studies in the mushroom and brush regimes [J].
Bartucci, R ;
Pantusa, M ;
Marsh, D ;
Sportelli, L .
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES, 2002, 1564 (01) :237-242
[4]   BSA adsorption on bimodal PEO brushes [J].
Bosker, WTE ;
Iakovlev, PA ;
Norde, W ;
Stuart, MAC .
JOURNAL OF COLLOID AND INTERFACE SCIENCE, 2005, 286 (02) :496-503
[5]   Canonical sampling through velocity rescaling [J].
Bussi, Giovanni ;
Donadio, Davide ;
Parrinello, Michele .
JOURNAL OF CHEMICAL PHYSICS, 2007, 126 (01)
[6]   Pharmacokinetic and biodistribution properties of poly(ethylene glycol)-protein conjugates [J].
Caliceti, P ;
Veronese, FM .
ADVANCED DRUG DELIVERY REVIEWS, 2003, 55 (10) :1261-1277
[7]   Selective protein interactions with phosphatidylserine containing liposomes alter the steric stabilization properties of poly(ethylene glycol) [J].
Chiu, GNC ;
Bally, MB ;
Mayer, LD .
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES, 2001, 1510 (1-2) :56-69
[8]   Tethered polymer chains: surface chemistry and their impact on colloidal and surface properties [J].
Currie, EPK ;
Norde, W ;
Stuart, MAC .
ADVANCES IN COLLOID AND INTERFACE SCIENCE, 2003, 100 :205-265
[9]   Stuffed brushes: theory and experiment [J].
Currie, EPK ;
Van der Gucht, J ;
Borisov, OV ;
Stuart, MAC .
PURE AND APPLIED CHEMISTRY, 1999, 71 (07) :1227-1241
[10]   Non-viral gene delivery systems [J].
Davis, ME .
CURRENT OPINION IN BIOTECHNOLOGY, 2002, 13 (02) :128-131