title: Effect of Statins on the Nanomechanical Properties of Supported Lipid Bilayers.
abstract: Many drugs and other xenobiotics may reach systemic concentrations where they interact not only with the proteins that are their therapeutic targets but also modify the physicochemical properties of the cell membrane, which may lead to altered function of many transmembrane proteins beyond the intended targets. These changes in bilayer properties may contribute to nonspecific, promiscuous changes in membrane protein and cell function because membrane proteins are energetically coupled to their host lipid bilayer. It is thus important, for both pharmaceutical and biophysical reasons, to understand the bilayer-modifying effect of amphiphiles (including therapeutic agents). Here we use atomic force microscopy topography imaging and nanomechanical mapping to monitor the effect of statins, a family of hypolipidemic drugs, on synthetic lipid membranes. Our results reveal that statins alter the nanomechanical stability of the bilayers and increase their elastic moduli depending on the lipid bilayer order. Our results also suggest that statins increase bilayer heterogeneity, which may indicate that statins form nanometer-sized aggregates in the membrane. This is further evidence that changes in bilayer nanoscale mechanical properties may be a signature of lipid bilayer-mediated effects of amphiphilic drugs.
authors.affiliation: U1006 Institut National de la Santé et de la Recherche Médicale (INSERM), Université Aix-Marseille, Parc Scientifique et Technologique de Luminy, Marseille, France.
authors.forename: Lorena
authors.initials: L
authors.lastname: Redondo-Morata
authors.affiliation: Department of Physiology and Biophysics, Weill Cornell Medical College, New York, New York.
authors.forename: R
authors.initials: R
authors.lastname: Lea Sanford
authors.affiliation: Department of Physiology and Biophysics, Weill Cornell Medical College, New York, New York.
authors.forename: Olaf S
authors.initials: OS
authors.lastname: Andersen
authors.affiliation: U1006 Institut National de la Santé et de la Recherche Médicale (INSERM), Université Aix-Marseille, Parc Scientifique et Technologique de Luminy, Marseille, France. Electronic address: simon.scheuring@inserm.fr.
authors.forename: Simon
authors.initials: S
authors.lastname: Scheuring
mesh_terms: D015060:1,2-Dipalmitoylphosphatidylcholine / Q000378:metabolism; D001696:Biomechanical Phenomena / Q000187:drug effects; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D004548:Elasticity / Q000187:drug effects; D057927:Hydrophobic and Hydrophilic Interactions; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D008051:Lipid Bilayers / Q000378:metabolism*; D055595:Mechanical Phenomena / Q000187:drug effects*; D010713:Phosphatidylcholines / Q000378:metabolism
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008051:Lipid Bilayers; D010713:Phosphatidylcholines; D015060:1,2-Dipalmitoylphosphatidylcholine; C017251:1,2-oleoylphosphatidylcholine