Perturbation lipid bilayer by probing molecule: Insights from molecular dynamics simulations of NBD-labeled lipids

Nitrobenzoxadiazole (NBD)-labeled lipids serve as an invaluable tool for investigating lipid behaviors and membrane properties by using their inherent fluorescence properties. Nevertheless, the precise impact of NBD-labeled lipids on membranes remains an area of considerable uncertainty. In this work, we performed the united atom molecular dynamics (MD) simulations to comprehensively explore the influence of 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine-N-(7-nitro-2-1,3-benzoxadiazol-4-yl) (18:1 NBD-PE) on the 1-palmitoyl-2-oleoyl-glycero-3-phosphocholine (POPC) lipid bilayers. The concentrations of NBD in the POPC lipid bilayer systems are systematically varied from 0 to 100 % with 16 different systems with total simulation time over 8 μs. The results showed the concentration-dependent effects of 18:1NBD-PE on both bilayer thickness and the area per lipid. As the increase of 18:1NBD-PE concentration in the bilayer, the order parameter of POPC lipid tail is significantly increased, resulting in an increase in area compressibility modulus. Interestingly, the presence of 18:1NBD-PE in the bilayer directly interacted with the unsaturated lipid chains and decreased the lateral diffusion coefficients. In summary, this study can provide the substantial perturbation of the fluorescence molecular probe on the lipid bilayers.