Will C-Laurdan dethrone Laurdan in fluorescent solvent relaxation techniques for lipid membrane studies?

Development of fluorescence methods involves the necessity of understanding the fluorescent probes behavior in their ground and excited states. In the case of biological membranes, the position of the dyes in the lipid bilayer and their response after excitation are necessary parameters to correctly analyze the experiments. In the present work, we focus on two fluorescent markers, Laurdan (6-lauroyl-2-(N,N-dimethylamino)naphthalene) and its derivative C-Laurdan (6-dodecanoyl-2-[N-methyl-N-(carboxymethyl)amino]naphthalene), recently proposed for lipid raft visualization [Kim, H. M.; et al. ChemBioChem 2007, 8, 553]. C-Laurdan, by the presence of an additional carboxyl group, has an advantage over Laurdan since it has a higher sensitivity to the membrane polarity at the lipid headgroup region and a higher water solubility. This theoretical study, based on quantum mechanical (QM) and molecular dynamics (MD) simulations in a fully hydrated lipid membrane model, compare the equilibrium and dynamic properties of both probes taking into account their fluorescence lifetimes. C-Laurdan is found to be more stable than Laurdan in the headgroup region of the membrane and also much more aligned with the lipids. This study suggests that, besides the lipid raft imaging, the C-Laurdan marker can considerably extend the capabilities of fluorescent solvent relaxation method.