Translocation of Endo-Functionalized Molecular Tubes across Different Lipid Bilayers: Atomistic Molecular Dynamics Simulation Study

Various artificial receptors, such as calixarenes, cyclodextrins, cucurbit[n]urils, and their acyclic compounds, pliiar[n]arenes, deep cavitands, and molecular tweezers, can permeate the lipid membranes and they are used as drug carriers to improve the drug solubility, stability, and bioavailability. Inspired by these, we have employed atomistic molecular dynamics simulation to examine the effects of endo-functionalized molecular tubes or naphthotubes (host-1a and host-1b) on seven different types of model lipid bilayers and the permeation properties of these receptors through these model lipid bilayers. Lipid types include six model lipid bilayers (POPC, POPE, DOPC, POPG, DPPE, POPE/POPG) and one realistic membrane (Yeast). We observe that these receptors are spontaneously translocated toward these model lipid bilayer head regions and do not proceed further into these lipid bilayer tail regions (reside at the interface between lipid head and lipid tail region), except for the DPPE-containing systems. In the DPPE model lipid bilayer-containing systems (1a-dppe and 1b-dppe), receptor molecules are only adsorbed on the bilayer surface and reside at the interface between lipid head and water. This finding is also supported by the biased free-energy profiles of these translocation processes. Passive transport of these receptors may be possible through these model lipid bilayers (due to low barrier height), except for DPPE bilayer-containing systems (that have a very high energy barrier at the center). The results from these simulations provide insight into the biocompatibility of host-1a or host-1b in microscopic detail. Based on this work, more research is needed to fully comprehend the role of these synthesized receptors as a prospective drug carrier.