This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Venturoli, M. Articles by Sperotto, M. M. Search for Related Content PubMed PubMed Citation Articles by Venturoli, M. Articles by Sperotto, M. M.

Simulation Studies of Protein-Induced Bilayer Deformations, and Lipid-Induced Protein Tilting, on a Mesoscopic Model for Lipid Bilayers with Embedded Proteins

Maddalena Venturoli ^* , Berend Smit ^* and Maria Maddalena Sperotto 

^* Department of Chemical Engineering, University of Amsterdam, Amsterdam, The Netherlands; Department of Chemistry, University College, London, United Kingdom; and Biocentrum, The Technical University of Denmark, Kgs. Lyngby, Denmark

Correspondence: Address reprint requests to Maria Maddalena Sperotto, E-mail: maria{at}cbs.dtu.dk.

Biological membranes are complex and highly cooperative structures. To relate biomembrane structure to their biological function it is often necessary to consider simpler systems. Lipid bilayers composed of one or two lipid species, and with embedded proteins, provide a model system for biological membranes. Here we present a mesoscopic model for lipid bilayers with embedded proteins, which we have studied with the help of the dissipative particle dynamics simulation technique. Because hydrophobic matching is believed to be one of the main physical mechanisms regulating lipid-protein interactions in membranes, we considered proteins of different hydrophobic length (as well as different sizes). We studied the cooperative behavior of the lipid-protein system at mesoscopic time- and lengthscales. In particular, we correlated in a systematic way the protein-induced bilayer perturbation, and the lipid-induced protein tilt, with the hydrophobic mismatch (positive and negative) between the protein hydrophobic length and the pure lipid bilayer hydrophobic thickness. The protein-induced bilayer perturbation was quantified in terms of a coherence length, _P, of the lipid bilayer hydrophobic thickness profile around the protein. The dependence on temperature of _P, and the protein tilt-angle, were studied above the main-transition temperature of the pure system, i.e., in the fluid phase. We found that _P depends on mismatch, i.e., the higher the mismatch is, the longer _P becomes, at least for positive values of mismatch; a dependence on the protein size appears as well. In the case of large model proteins experiencing extreme mismatch conditions, in the region next to the so-called lipid annulus, there appears an undershooting (or overshooting) region where the bilayer hydrophobic thickness is locally lower (or higher) than in the unperturbed bilayer, depending on whether the protein hydrophobic length is longer (or shorter) than the pure lipid bilayer hydrophobic thickness. Proteins may tilt when embedded in a too-thin bilayer. Our simulation data suggest that, when the embedded protein has a small size, the main mechanism to compensate for a large hydrophobic mismatch is the tilt, whereas large proteins react to negative mismatch by causing an increase of the hydrophobic thickness of the nearby bilayer. Furthermore, for the case of small, peptidelike proteins, we found the same type of functional dependence of the protein tilt-angle on mismatch, as was recently detected by fluorescence spectroscopy measurements.

This article has been cited by other articles:

				F. J.-M. de Meyer, M. Venturoli, and B. Smit Molecular Simulations of Lipid-Mediated Protein-Protein Interactions Biophys. J., August 15, 2008; 95(4): 1851 - 1865. [Abstract] [Full Text] [PDF]

				S. Esteban-Martin and J. Salgado The Dynamic Orientation of Membrane-Bound Peptides: Bridging Simulations and Experiments Biophys. J., December 15, 2007; 93(12): 4278 - 4288. [Abstract] [Full Text] [PDF]

				D. Constantin, G. Brotons, A. Jarre, C. Li, and T. Salditt Interaction of Alamethicin Pores in DMPC Bilayers Biophys. J., June 1, 2007; 92(11): 3978 - 3987. [Abstract] [Full Text] [PDF]

				G. Brannigan and F. L. H. Brown Contributions of Gaussian Curvature and Nonconstant Lipid Volume to Protein Deformation of Lipid Bilayers Biophys. J., February 1, 2007; 92(3): 864 - 876. [Abstract] [Full Text] [PDF]

				S. K. Kandasamy and R. G. Larson Molecular Dynamics Simulations of Model Trans-Membrane Peptides in Lipid Bilayers: A Systematic Investigation of Hydrophobic Mismatch Biophys. J., April 1, 2006; 90(7): 2326 - 2343. [Abstract] [Full Text] [PDF]

				G. Brannigan and F. L. H. Brown A Consistent Model for Thermal Fluctuations and Protein-Induced Deformations in Lipid Bilayers Biophys. J., March 1, 2006; 90(5): 1501 - 1520. [Abstract] [Full Text] [PDF]

				S. O. Nielsen, B. Ensing, V. Ortiz, P. B. Moore, and M. L. Klein Lipid Bilayer Perturbations around a Transmembrane Nanotube: A Coarse Grain Molecular Dynamics Study Biophys. J., June 1, 2005; 88(6): 3822 - 3828. [Abstract] [Full Text] [PDF]