BIOPHYSICAL THEORY AND MODELING |
Structure and Dynamics of Model Pore Insertion into a Membrane
Carlos F Lopez 1, Steve O Nielsen 2, Bernd Ensing 2, Preston B Moore 3 and Michael L Klein 2*
1 University of Texas, Austin
2 University of Pennsylvania
3 University of the Sciences in Philadelphia
* To whom correspondence should be addressed. E-mail: klein{at}lrsm.upenn.edu.
Submitted on September 30, 2004
Revised on November 22, 2004
Accepted on 6 January 2005
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Abstract |
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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 head group/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 (Lopez et al., P.N.A.S. 101:4431-4434 (2004)). The hydrophobic tube submerges into the membrane core in a carpet-like manner. The capped tube laterally fuses with the closest leaflet, and then, after plunging into the membrane interior, rotates to assume a trans-bilayer orientation. Two lipids become trapped at the end of the tube as it penetrates the membrane. The hydrophilic head groups 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.
Key Words:
hydrophilic/hydrophobic matching, lipid flip-flop, membrane insertion, transmembrane pore, water permeation
