379563 Acceleration of Transport Across Lipid Membranes By the Membrane Undulations: A Systematic Investigation of Effects of Membrane Composition
Transport of small molecules and nanoparticles across lipid bilayers plays an important role in various biological processes and technological applications. The rate of this transport is determined in part by the height of the energy barrier, which depends on the solute affinity for the solvent and head- and tail-groups of lipids comprising the bilayer. An additional factor affecting the transport rate is dynamics of the membrane undulations. As the solute approaches an energy barrier inside the membrane, the membrane deforms towards the solute. This accelerates the process of crossing of the energy barrier since long wavelength membrane undulations experience a smaller friction than the solute translocating through the membrane.
Details of this cooperative solute-membrane mechanism are investigated using a multi-dimensional Langevin equation containing an explicit model for the membrane undulation modes. The results of the theoretical analysis are validated by coarse grained molecular dynamics simulations of a hydrophobic nanoparticle crossing a lipid bilayer. Two series of the simulations were performed: (1) transport through a freely undulating membrane and (2) transport through a membrane with constrained undulations. It is observed that transport through the freely undulating membrane is faster than through the restrained membrane and the acceleration factor is consistent with the theoretical prediction.
After the theory is validated by the simulations, it is applied to analysis of transport through lipid membranes of various compositions. The membrane composition affects elastic properties of the membrane and, hence, dynamics of the membrane undulation. Therefore, it is expected to affect the undulation-induced acceleration of the solute transport. Effects of the length of lipid tails, number of unsaturated bonds in the tails, and presence of cholesterol in the membrane are investigated.