Effect of Acyl Chain Length on the Rate of Phospholipid Flip-Flop and Intermembrane Transfer

The rate at which phospholipids equilibrate between different membranes and between the non-polar environments in biological fluids is of high importance in the understanding of biomembrane diversity, as well as in the development of liposomes for drug delivery. In this work, we characterize the rate of insertion into and desorption from POPC bilayers for a homologous series of amphiphiles with the fluorescent NBD group attached to phosphoethanolamines of different acyl chain lengths, NBD-diC _n -PE with n = 6, 8, 10, and 12. The rate of translocation between bilayer leaflets was also characterized, providing all the relevant parameters for their interaction with lipid bilayers. The results are complemented with data for NBD-diC₁₄-PE obtained from literature (Abreu et al. Biophys J 87:353-365, 2004; Moreno et al. Biophys J 91:873-881, 2006). The rate of translocation between the POPC leaflets is not dependent on the length of the acyl chains, while this affects strongly the rate of desorption from the bilayer. Insertion in the POPC bilayer is not diffusion controlled showing a significant dependence on the acyl chain length and on temperature. The results obtained are compared with those previously reported for NBD-LysoC₁₄-PE (Sampaio et al. Biophys J 88:4064-4071, 2005), and with the homologous series of single chain amphiphiles NBD-C _n (Cardoso et al. J Phys Chem B 114:16337-16346, 2010; J Phys Chem B 115:10098-10108, 2011). This allows the establishment of important relations between the rate constants for interaction with the lipid bilayers and the structural properties of the amphiphiles, namely the total surface and the cross-section of their non-polar region.