title: Coarse-grained model for PEGylated lipids: effect of PEGylation on the size and shape of self-assembled structures.
abstract: Self-assembly of polyethylene glycol (PEG)-grafted lipids at different sizes and concentrations was simulated using the MARTINI coarse-grained (CG) force field. The interactions between CG PEG and CG dipalmitoylglycerophosphocholine (DPPC)-lipids were parametrized by matching densities of 19-mers of PEG and polyethylene oxide (PEO) grafted to the bilayer from all-atom simulations. Mixtures of lipids and PEG-grafted (M(w) = 550, 1250, and 2000) lipids in water self-assembled to liposomes, bicelles, and micelles at different ratios of lipids and PEGylated lipids. Average aggregate sizes decrease with increasing PEGylated-lipid concentration, in qualitative agreement with experiment. PEGylated lipids concentrate at the rims of bicelles, rather than at the planar surfaces; this also agrees with experiment, though the degree of segregation is less than that assumed in previous modeling of the experimental data. Charged lipids without PEG evenly distribute at the rim and planar surfaces of the bicelle. The average end-to-end distances of the PEG on the PEGylated lipids are comparable in liposomes, bicelles (edge or planar surface), and micelles and only slightly larger than for an isolated PEG in solution. The ability of PEGylated lipids to induce the membrane curvature by the bulky headgroup with larger PEG, and thereby modulate the phase behavior and size of lipid assemblies, arises from their relative concentration.
authors: Department of Chemical Engineering, Dankook University, Yongin, 448-701, South Korea. leeh@dankook.ac.kr
authors: Hwankyu
authors: H
authors: Lee
authors: Richard W
authors: RW
authors: Pastor
references: J Chem Theory Comput. 2008 Mar;4(3):435-47
references: 26620784
references: Biochim Biophys Acta. 2008 Oct;1778(10):2210-6
references: 18571494
references: J Phys Chem B. 2009 Nov 19;113(46):15170-80
references: 19905021
references: Clin Pharmacokinet. 2001;40(7):539-51
references: 11510630
references: Adv Drug Deliv Rev. 2002 Jun 17;54(4):459-76
references: 12052709
references: J Colloid Interface Sci. 2004 May 1;273(1):148-54
references: 15051444
references: J Comput Chem. 2009 Jul 30;30(10):1545-614
references: 19444816
references: Bioconjug Chem. 2007 May-Jun;18(3):663-70
references: 17375896
references: AAPS J. 2007 Jun 08;9(2):E171-80
references: 17614359
references: Chem Phys Lipids. 2005 Jun;135(2):223-44
references: 15921980
references: J Phys Chem B. 2009 Oct 8;113(40):13186-94
references: 19754083
references: Biophys J. 2001 Oct;81(4):2163-71
references: 11566787
references: J Phys Chem B. 2010 May 27;114(20):6836-49
references: 20438090
references: Biochim Biophys Acta. 2007 May;1768(5):1160-9
references: 17320042
references: Biochim Biophys Acta. 1982 Aug 25;690(1):15-9
references: 7126566
references: Biochim Biophys Acta. 2007 Oct;1768(10):2578-85
references: 17662233
references: J Mol Graph. 1996 Feb;14(1):33-8, 27-8
references: 8744570
references: Biophys Chem. 2008 Feb;132(2-3):97-103
references: 18006210
references: Biophys J. 2008 Aug;95(4):1590-9
references: 18456821
references: Bioconjug Chem. 2007 Mar-Apr;18(2):456-68
references: 17326672
references: Biophys Chem. 2001 Oct 18;93(1):11-22
references: 11604213
references: Int J Pharm. 2003 May 12;257(1-2):111-24
references: 12711167
references: Bioconjug Chem. 2008 Aug;19(8):1660-72
references: 18610944
references: Phys Rev A Gen Phys. 1985 Mar;31(3):1695-1697
references: 9895674
references: Proc Natl Acad Sci U S A. 2007 Jan 30;104(5):1482-7
references: 17244708
references: Phys Chem Chem Phys. 2010 Feb 21;12(7):1589-94
references: 20126774
references: J Chem Theory Comput. 2007 May;3(3):1120-33
references: 26627431
references: Crit Rev Ther Drug Carrier Syst. 1992;9(3-4):249-304
references: 1458545
references: Biochemistry. 1980 Feb 19;19(4):601-15
references: 7356951
references: Bioconjug Chem. 2008 Nov 19;19(11):2280-4
references: 18844391
references: Biophys J. 2003 Dec;85(6):3839-47
references: 14645073
references: Biophys J. 1995 May;68(5):1921-36
references: 7612834
references: Biomacromolecules. 2009 Apr 13;10(4):784-92
references: 19281149
references: J Phys Chem B. 2010 Jun 17;114(23):7830-43
references: 20496934
references: Nat Rev Drug Discov. 2003 Mar;2(3):214-21
references: 12612647
references: J Phys Chem B. 2008 Mar 13;112(10):2888-900
references: 18275181
references: Phys Chem Chem Phys. 2009 Mar 28;11(12):2056-67
references: 19280016
references: Biochim Biophys Acta. 1998 Jun 29;1376(1):91-145
references: 9666088
references: Pharm Res. 2007 Jan;24(1):1-16
references: 17109211
references: Biophys J. 2003 Jan;84(1):350-5
references: 12524288
references: Nanotechnology. 2009 Mar 11;20(10):105103
references: 19417510
references: J Phys Chem B. 2007 Jul 12;111(27):7812-24
references: 17569554