Fluctuation-Driven Molecular Transport Through an Asymmetric Membrane Channel

Channel proteins that selectively conduct molecules across cell membranes often exhibit an asymmetric structure. By means of a stochastic model, we argue that channel asymmetry in the presence of nonequilibrium fluctuations, fueled by the cell’s metabolism as observed recently, can dramatically influence the transport through such channels by a ratchetlike mechanism. For an aquaglyceroporin that conducts water and glycerol, we show that a previously determined asymmetric glycerol potential leads to enhanced inward transport of glycerol, but for unfavorably high glycerol concentrations also to enhanced outward transport that protects a cell against poisoning.

Figure 1

Section through the glycerol conduction pathway in GlpF and the corresponding asymmetric PMF (solid curve) reported in 8.

Figure 2

(a) Ratio of outward and inward glycerol fluxes in GlpF as function of a constant force $F_0$. (b)–(c) Transport induced by a square-wave force in GlpF. Shown are the inward [$p_1=0$], outward [$p_0=0$], and equal concentration [$p_1=p_0$] fluxes vs force amplitude $F_0$. (d) Ratio of the inner to outer glycerol concentrations vs $F_0$ for vanishing flux.

Figure 3

Contour density plots of the numerically evaluated relative (a) inward $J(F_0,T_0|p_0,0)/J_0$, (b) outward $-J(F_0,T_0|0,p_0)/J_0$, and (c) equal concentration $-J(F_0,T_0|p_0,p_0)/J_0$ glycerol fluxes in GlpF as a function of the amplitude $F_0$ and mean switching time $T_0$ of the RTF; $J_0\equiv J(0,T_0|p_0,0)$ is the inward flux in the absence of the RTF.

Figure 4

Contour density plot of the concentration ratio $p_1/p_0={\mathcal{A}}_0/{\mathcal{A}}_1$ at which current reversal ($J=0$) takes place in GlpF subjected to RTF.