How to link pyrene to its host lipid to minimize the extent of membrane perturbations and to optimize pyrene dimer formation.
We study how lipid probes based on pyrene-labeling could be designed to minimize perturbations in lipid bilayers, and how the same design principles could be exploited to develop probes which gauge lipid dynamics primarily within a single lipid monolayer or between them. To this end, we use atomistic molecular dynamics simulations to consider membranes where pyrene moieties are attached to lipid acyl chains in varying positions. We find that in a DOPC bilayer the conformational ordering of lipids around di-pyrenyl-PC probes is altered to a largely similar extent regardless of where the pyrene moiety is attached to the hydrocarbon chain. This is in contrast to saturated membranes, where pyrene-induced perturbations have been observed to be more prominent. Meanwhile, the formation of pyrene dimers depends on the linkage point between pyrene and its host lipid. Membrane-spanning dimers between lipids in different membrane leaflets are observed only if the pyrene moiety is attached to the latter half of the acyl chain. A seemingly minor change to link pyrene to an acyl chain that is two carbons shorter leads to a situation where membrane-spanning dimers are no longer observed. Further, simulations suggest that formation of dimers is a slow process, where the rate is limited by both lateral diffusion and the dimerization process once the two probes are neighbors to one another. Typical lifetimes of pyrene dimers turn out be of the order of nanoseconds. The results are expected to pave the way for designing ways to consider experimentally topics such as intraleaflet lateral diffusion, motion of lipids within and between membrane domains, and membrane domain registration across bilayers.
Department of Chemical Physics and Optics, Faculty of Mathematics and Physics, Charles University, Ke Karlovu 3, Prague 2 CZ-12116, Czech Republic.
Miroslava Dékány
MD
Fraňová
Department of Physics, Tampere University of Technology, P.O. Box 692, FI-33101 Tampere, Finland.
Jarmila
J
Repáková
Helsinki Eye Lab, Department of Ophthalmology, University of Helsinki, Helsinki, Finland.
Juha M
JM
Holopainen
Department of Physics, Tampere University of Technology, P.O. Box 692, FI-33101 Tampere, Finland; MEMPHYS - Center for Biomembrane Physics, University of Southern Denmark, Odense, Denmark. Electronic address: Ilpo.Vattulainen@tut.fi.
Ilpo
I
Vattulainen
D002462:Cell Membrane / Q000737:chemistry / Q000187:drug effects*; D019281:Dimerization; D005456:Fluorescent Dyes / Q000737:chemistry / Q000494:pharmacology; D006838:Hydrocarbons / Q000737:chemistry; D008051:Lipid Bilayers / Q000737:chemistry*; D008563:Membrane Lipids / Q000737:chemistry*; D011721:Pyrenes / Q000737:chemistry* / Q000494:pharmacology*; D013997:Time Factors
D005456:Fluorescent Dyes; D006838:Hydrocarbons; D008051:Lipid Bilayers; D008563:Membrane Lipids; D011721:Pyrenes; C030984:pyrene
Bis-pyrene; Fluorescent probe; Lipid bilayer; Lipid membrane; Molecular dynamics simulation; Pyrene