Deconvoluting the Effect of the Hydrophobic and Hydrophilic
Domains of an Amphiphilic Integral Membrane Protein in Lipid Bicontinuous
Cubic Mesophases
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Abstract
Lipidic bicontinuous cubic mesophases
with encapsulated amphiphilic
proteins are widely used in a range of biological and biomedical applications,
including in meso crystallization, as drug delivery vehicles for therapeutic
proteins, and as biosensors and biofuel cells. However, the effect
of amphiphilic protein encapsulation on the cubic phase nanostructure
is not well-understood. In this study, we illustrate the effect of
incorporating the bacterial amphiphilic membrane protein Ag43, and
its individual hydrophobic β<sup>43</sup> and hydrophilic α<sup>43</sup> domains, in bicontinuous cubic mesophases. For the monoolein,
monoalmitolein, and phytantriol cubic phases with and without 8% w/w
cholesterol, the effect of the full length amphiphilic protein Ag43
on the cubic phase nanostructure was more significant than the sum
of the individual hydrophobic β<sup>43</sup> and hydrophilic
α<sup>43</sup> domains. Several factors were found to potentially
influence the impact of the hydrophobic β<sup>43</sup> domain
on the cubic phase internal nanostructure. These include the size
of the hydrophobic β<sup>43</sup> domain relative to the thickness
of the lipid bilayer, as well as its charge and diameter. The size
of the hydrophilic α<sup>43</sup> domain relative to the water
channel radius of the cubic mesophase was also found to be important.
The secondary structure of the Ag43 proteins was affected by the hydrophobic
thickness and physicochemical properties of the lipid bilayer and
the water channel diameter of the cubic phase. Such structural changes
may be small but could potentially affect membrane protein function