Limited Perturbation of a DPPC Bilayer by Fluorescent Lipid Probes: A Molecular Dynamics Study

Abstract: The presence and the properties of lipid bilayer nanometer-scale domains might be important for understanding the membranes of living cells. We used molecular dynamics (MD) simulations to investigate perturbations of a small patch of fluid-phase DPPC bilayer upon incorporation of fluorescent indocarbocyanine lipid probes commonly used to study membranes (DiI-C12:0, DiI-C18:0, or DiI-C18:2). In simulations containing 1 probe per 64 total lipids in each leaflet, an 8 - 12% decrease in chain order is observed for DPPC molecules in the solvation shell closest to the probe, relative to a pure DPPC bilayer. A ~5% increase in chain order is seen in the next three shells, resulting in a small overall increase in average DPPC chain order. In simulations with 1 probe per 256 total lipids in each leaflet, average DPPC chain order is unaffected by the probe. Thus, these DiI probes cause an oscillatory perturbation of their local environment but do not strongly influence the average properties of even "nanoscopic" lipid phase domains.