A physical mechanism for large-ion selectivity of ion channels

Many biological ion channels preferentially conduct large ions over small ions. Here we propose a simple mechanism for this large-particle selectivity. Size selectivity is examined using a hard-sphere model of a binary fluid in a two-compartment system that represents a bath and the selective section of a channel (filter). The solvent is assigned a small repulsive excess chemical potential in the filter. Under these conditions, larger solutes are absorbed into the filter in greater numbers than small solutes because of a negative pressure difference between the filter and the bath. To model the selectivity of ion channels, we extend the model to a hard-sphere electrolyte and a filter that contains, in addition to particles exchanged with the bath, structural ions that are confined to the filter and introduce charge selectivity. This system also selects for the larger ions. For this system, the pressure in the filter varies greatly as a function of bath concentration. Because this would result in large forces acting on the channel protein, we also consider a constant-pressure system and allow the volume to vary. In that case, we observe ion concentration-dependent increases in filter volume and ion density that result in conductance properties observed in some channels.