Interactions of Small Molecules with Membranes: Partitioning, Permeability, and Electrical Effects

Abstract

At the beginning of the previous chapter, the point was made that biomembranes are not merely passive barriers defining the boundaries of cells or organelles. In this chapter, we recognize that, in fact, being a barrier to solute flux between aqueous compartments is an essential part of membrane function. The major focus of this chapter is the interaction between the phospholipid bilayer and small solute molecules, both ions and nonelectrolytes. We will first discuss the binding of small molecules to the membrane, either adsorbed at the surface or partitioning into the interior of the bilayer. Any solute that can partition into the membrane can diffuse across the bilayer and exit from the opposite side. Membrane permeability to nonelectrolytes is discussed in this context. In order to understand the way in which ions interact with the membrane, the total electric potential energy profile of the membrane must be considered. The electrical component of the free energy of an ion near or within the membrane is critical not only for understanding how divalent and monovalent metal ions bind to the membrane surface, but also for estimating the local pH at the membrane surface, and for modeling how some enzymes and ion channels might be regulated by a voltage across the bilayer.