title: Interaction of fullerene nanoparticles with biomembranes: from the partition in lipid membranes to effects on mitochondrial bioenergetics.
abstract: Partition and localization of C60 and its derivative C60(OH)18-22 in lipid membranes and their impact on mitochondrial activity were studied, attempting to correlate those events with fullerene characteristics (size, surface chemistry, and surface charge). Fluorescence quenching studies suggested that C60(OH)18-22 preferentially populated the outer regions of the bilayer, whereas C60 preferred to localize in deeper regions of the bilayer. Partition coefficient values indicated that C60 exhibited higher affinity for dipalmitoylphosphatidylcholine and mitochondrial membranes than C60(OH)18-22. Both fullerenes affected the mitochondrial function, but the inhibitory effects promoted by C60 were more pronounced than those induced by C60(OH)18-22 (up to 20 nmol/mg of mitochondrial protein). State 3 and p-trifluoromethoxyphenylhydrazone-uncoupled respirations are inhibited by both fullerenes when glutamate/malate or succinate was used as substrate. Phosphorylation system and electron transport chain of mitochondria are affected by both fullerenes, but only C60 increased the inner mitochondrial membrane permeability to protons, suggesting perturbations in the structure and dynamics of that membrane. At concentrations of C60(OH)18-22 above 20 nmol/mg of mitochondrial protein, the activity of FoF1-ATP synthase was also decreased. The evaluation of transmembrane potential showed that the mitochondria phosphorylation cycle decreased upon adenosine diphosphate addition with increasing fullerenes concentration and the time of the repolarization phase increased as a function of C60(OH)18-22 concentration. Our results suggest that the balance between hydrophilicity and hydrophobicity resulting from the surface chemistry of fullerene nanoparticles, rather than the cluster size or the surface charge acquired by fullerenes in water, influences their membrane interactions and consequently their effects on mitochondrial bioenergetics.
authors.affiliation: * CNC-Center for Neuroscience and Cell Biology, 3004-517 Coimbra.
authors.forename: Sandra M
authors.initials: SM
authors.lastname: Santos
authors.forename: Augusto M
authors.initials: AM
authors.lastname: Dinis
authors.forename: Francisco
authors.initials: F
authors.lastname: Peixoto
authors.forename: Lino
authors.initials: L
authors.lastname: Ferreira
authors.forename: Amália S
authors.initials: AS
authors.lastname: Jurado
authors.forename: Romeu A
authors.initials: RA
authors.lastname: Videira
mesh_terms: D000818:Animals; D004734:Energy Metabolism / Q000187:drug effects*; D037741:Fullerenes / Q000737:chemistry / Q000633:toxicity*; D066298:In Vitro Techniques; D007425:Intracellular Membranes / Q000187:drug effects* / Q000378:metabolism; D008051:Lipid Bilayers / Q000378:metabolism*; D008297:Male; D008563:Membrane Lipids / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D046529:Microscopy, Electron, Transmission; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000378:metabolism; D053758:Nanoparticles; D010101:Oxygen Consumption / Q000187:drug effects; D010316:Particle Size; D051381:Rats; D017208:Rats, Wistar; D013050:Spectrometry, Fluorescence; D013499:Surface Properties
chemical_list: D037741:Fullerenes; D008051:Lipid Bilayers; D008563:Membrane Lipids
keywords: carbon nanoparticles; fullerenes; membrane partition.; mitochondria