Archaeal-Inspired Lipids Exhibit Low Membrane Permeability Due To Entropic Effects

Many archaea are able to withstand extremes of temperature, pressure, pH and/or levels of salt. One unique feature of these extremophiles that gives them this capability is that their membranes are made from covalently linked, tetraether lipids that form a monolayer rather than a traditional bilayer. Here we present experimental and computational results on a series of synthetic archaeal-inspired lipids, looking at their biophysical properties and rates of permeation. Apart from a number of interesting mechanical and material properties, we find that tethered lipids exhibit a much stronger dependence on the entropy of activation for small molecules to cross the membrane. In relating our measured permeation rates with properties of the membrane, we find that the order parameters for the lipid tails describe the changes in entropy, and the combination of area per lipid, membrane thickness and short-range diffusion coefficient can predict our permeation results. Interestingly, we also see that the rates of water penetration into the core of the membrane provide an excellent empirical measure that matches our experimental permeation rates.