title: Lateral diffusion of membrane proteins: consequences of hydrophobic mismatch and lipid composition.
abstract: Biological membranes are composed of a large number lipid species differing in hydrophobic length, degree of saturation, and charge and size of the headgroup. We now present data on the effect of hydrocarbon chain length of the lipids and headgroup composition on the lateral mobility of the proteins in model membranes. The trimeric glutamate transporter (GltT) and the monomeric lactose transporter (LacY) were reconstituted in giant unilamellar vesicles composed of unsaturated phosphocholine lipids of varying acyl chain length (14-22 carbon atoms) and various ratios of DOPE/DOPG/DOPC lipids. The lateral mobility of the proteins and of a fluorescent lipid analog was determined as a function of the hydrophobic thickness of the bilayer (h) and lipid composition, using fluorescence correlation spectroscopy. The diffusion coefficient of LacY decreased with increasing thickness of the bilayer, in accordance with the continuum hydrodynamic model of Saffman-Delbrück. For GltT, the mobility had its maximum at diC18:1 PC, which is close to the hydrophobic thickness of the bilayer in vivo. The lateral mobility decreased linearly with the concentration of DOPE but was not affected by the fraction of anionic lipids from DOPG. The addition of DOPG and DOPE did not affect the activity of GltT. We conclude that the hydrophobic thickness of the bilayer is a major determinant of molecule diffusion in membranes, but protein-specific properties may lead to deviations from the Saffman-Delbrück model.
authors.affiliation: Department of Biochemistry, Groningen Biomolecular Sciences and Biotechnology Institute, Netherlands Proteomics Centre and the Zernike Institute for Advanced Materials, University of Groningen, Nijenborgh, Groningen, The Netherlands.
authors.forename: Sivaramakrishnan
authors.initials: S
authors.lastname: Ramadurai
authors.forename: Ria
authors.initials: R
authors.lastname: Duurkens
authors.forename: Victor V
authors.initials: VV
authors.lastname: Krasnikov
authors.forename: Bert
authors.initials: B
authors.lastname: Poolman
mesh_terms: D027322:Amino Acid Transport System X-AG / Q000737:chemistry / Q000378:metabolism; D004058:Diffusion; D004926:Escherichia coli; D029968:Escherichia coli Proteins / Q000737:chemistry / Q000378:metabolism; D001411:Geobacillus stearothermophilus; D020404:Glycerophospholipids / Q000737:chemistry*; D057927:Hydrophobic and Hydrophilic Interactions; D008565:Membrane Proteins / Q000737:chemistry* / Q000378:metabolism*; D026901:Membrane Transport Proteins / Q000737:chemistry / Q000378:metabolism; D013050:Spectrometry, Fluorescence; D013499:Surface Properties; D053835:Unilamellar Liposomes / Q000737:chemistry
chemical_list: D027322:Amino Acid Transport System X-AG; D029968:Escherichia coli Proteins; D020404:Glycerophospholipids; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D053835:Unilamellar Liposomes; C021499:lactose permease
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