Regulation of Channel Function Due To Coupling With a Lipid Bilayer

Abstract

Regulation of membrane protein functions due to hydrophobic coupling with lipid bilayer is investigated. Binding energy between lipid bilayer and integral ion channel with different structures has been calculated considering 0th or 1st, 2nd, etc. order terms in the expansion of the screened Coulomb interaction Vsc(r)=integral of d3kExp{ik.r}Vsc(k) with Vsc(r) being the inverse Fourier transformation of the screened Coulomb interaction in Fourier space Vsc(k)=V(k)(1+f(n,T)V(k))−1 for bilayer thickness (d0) channel length (l) mismatch (d0-l) to be filled by none or single, double etc. lipids, respectively. V(k) is the direct Coulomb interaction (in Fourier space) between channels and lipids on the bilayer, f(n,T)=n/2kBT, n is the lipid density, T is absolute temperature and kB is Boltzmann's constant. We find that the hydrophobic bilayer thickness channel length mismatch d0-l induces channel destabilization exponentially while negative lipid curvature (c0) linearly. Lipid charge appears with dominant effects in case of higher mismatch. Experimental parameters related to gramicidin A (gA) and alamethicin (Alm) channel dynamics in black lipid membranes inside NaCl aqueous phases are consistent with theoretical predictions. Our experimental results (with others) show that average gA channel lifetime decreases exponentially with increasing d0-l but linearly with increasing negative c0. The Alm channel formation rate and relative free energy profiles between its different conductance levels follow identical trends as predicted by our theoretical results. This study provides a general framework for understanding the underlying mechanisms of membrane protein functions in biological systems.