Effect of Cholesterol on the Gramicidin A Induced Membrane Curvature and Order Parameter

The function and properties of a transmembrane (TM) protein depend on the membrane composition. Consequently, the membrane adaptation to the inserted protein can also be influenced by the said membrane composition. This work examines the impact of cholesterol (Chol) composition on the Gramicidin A (gA)-induced membrane curvature and order parameter (|S_CD|) of the lipids present in the membrane. The magnitude of the curvature was found to be dependent on the Chol concentration present in the membrane leaflet and resulted in countering the hydrophobic mismatch at the gA-membrane interface. Additionally, a minor reduction of the number of water molecules present in the channel and the formation of the previously proposed gA-Chol complex were noted. Using a four-region annular model, it was demonstrated that the bilayer thickness and |S_CD| around the gA were affected by the Chol concentration in a distance-dependent manner. The paralipidome was enhanced in Chol and 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine lipids, which may have resulted in the reduction of energy cost associated with forming the gA conduction channel and removing the hydrophobic mismatch between the membrane and the gA dimer. This work will help better understand the role of Chol in the membrane adaptation in the presence of TM proteins.