Structure and dynamics of model pore insertion into a membrane.
A cylindrical transmembrane molecule is constructed by linking hydrophobic sites selected from a coarse grain model. The resulting hollow tube assembly serves as a representation of a transmembrane channel, pore, or a carbon nanotube. The interactions of a coarse grain di-myristoyl-phosphatidyl-choline hydrated bilayer with both a purely hydrophobic tube and a tube with hydrophilic caps are studied. The hydrophobic tube rotates in the membrane and becomes blocked by lipid tails after a few tens of nanoseconds. The hydrophilic sites of the capped tube stabilize it by anchoring the tube in the lipid headgroup/water interfacial region of each membrane leaflet. The capped tube remains free of lipid tails. The capped tube spontaneously conducts coarse grain water sites; the free-energy profile of this process is calculated using three different methods and is compared to the barrier for water permeation through the lipid bilayer. Spontaneous tube insertion into an undisturbed lipid bilayer is also studied, which we reported briefly in a previous publication. The hydrophobic tube submerges into the membrane core in a carpetlike manner. The capped tube laterally fuses with the closest leaflet, and then, after plunging into the membrane interior, rotates to assume a transbilayer orientation. Two lipids become trapped at the end of the tube as it penetrates the membrane. The hydrophilic headgroups of these lipids associate with the lower tube cap and assist the tube in crossing the interior of the membrane. When the rotation is complete these lipids detach from the tube caps and fuse with the lower leaflet lipids.
Lopez
Carlos F
CF
Center for Molecular Modeling and Department of Chemistry, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Nielsen
Steve O
SO
Ensing
Bernd
B
Moore
Preston B
PB
Klein
Michael L
ML
D001665:Binding Sites; D001703:Biophysics / Q000379:methods*; D003198:Computer Simulation; D004058:Diffusion; D004134:Dimyristoylphosphatidylcholine / Q000737:chemistry; D008051:Lipid Bilayers / Q000737:chemistry; D008055:Lipids / Q000737:chemistry; D046911:Macromolecular Substances / Q000737:chemistry; D008566:Membranes / Q000737:chemistry; D008958:Models, Molecular; D008962:Models, Theoretical; D037742:Nanotubes, Carbon / Q000737:chemistry; D013816:Thermodynamics; D013997:Time Factors; D014867:Water / Q000737:chemistry
D008051:Lipid Bilayers; D008055:Lipids; D046911:Macromolecular Substances; D037742:Nanotubes, Carbon; D014867:Water; D004134:Dimyristoylphosphatidylcholine
Annu Rev Biophys Biomol Struct. 2002;31:207-33
11988468
Proc Natl Acad Sci U S A. 2004 Mar 30;101(13):4431-4
15070735
Biopolymers. 1998;47(6):415-33
10333735
FEBS Lett. 1998 May 8;427(2):267-70
9607325
Biophys J. 2004 Oct;87(4):2107-15
15454415
Proc Natl Acad Sci U S A. 1987 Aug;84(15):5449-53
3299384
Biophys J. 2000 Oct;79(4):2002-9
11023904
Trends Plant Sci. 2002 Jun;7(6):257-63
12049922
Biochemistry. 2000 Jul 25;39(29):8347-52
10913240
Biophys J. 2001 Apr;80(4):1837-50
11259297
Biophys J. 1999 Feb;76(2):618-30
9929468
Science. 1999 May 21;284(5418):1313-8
10334979
Nature. 2002 Jan 24;415(6870):389-95
11807545
Science. 2002 Jun 21;296(5576):2198-200
12077410
Curr Opin Biotechnol. 1999 Feb;10(1):94-103
10047514
Biochemistry. 2002 Apr 16;41(15):4946-52
11939790
Biochemistry. 2003 Jan 14;42(1):231-7
12515559
Nat Biotechnol. 2001 Jul;19(7):622-3
11433269
Nature. 2001 Jul 26;412(6845):452-5
11473322
Biophys J. 2001 Sep;81(3):1475-85
11509361
Biophys J. 2002 Mar;82(3):1176-89
11867436
Anal Chem. 2003 Dec 15;75(24):6861-7
14670046
Phys Rev Lett. 2002 Aug 5;89(6):064503
12190588
Biophys J. 2002 Sep;83(3):1259-67
12202353
Biophys J. 2001 Oct;81(4):2251-6
11566795
Biophys J. 2004 Jan;86(1 Pt 1):50-7
14695248
Acc Chem Res. 2002 Jun;35(6):438-46
12069629
Nature. 2001 Nov 8;414(6860):188-90
11700553
Proc Natl Acad Sci U S A. 2004 Aug 17;101(33):12177-82
15302940