Protein-mediated transformation of lipid vesicles into tubular networks

TY - JOUR

T1 - Protein-mediated transformation of lipid vesicles into tubular networks

AU - Simunovic, Mijo

AU - Mim, Carsten

AU - Marlovits, Thomas C

AU - Resch, Guenter

AU - Unger, Vinzenz M

AU - Voth, Gregory A

N1 - Copyright © 2013 Biophysical Society. Published by Elsevier Inc. All rights reserved.

PY - 2013/8/6

Y1 - 2013/8/6

N2 - Key cellular processes are frequently accompanied by protein-facilitated shape changes in the plasma membrane. N-BAR-domain protein modules generate curvature by means of complex interactions with the membrane surface. The way they assemble and the mechanism by which they operate are largely dependent on their binding density. Although the mechanism at lower densities has recently begun to emerge, how membrane scaffolds form at high densities remains unclear. By combining electron microscopy and multiscale simulations, we show that N-BAR proteins at high densities can transform a lipid vesicle into a 3D tubular network. We show that this process is a consequence of excess adhesive energy combined with the local stiffening of the membrane, which occurs in a narrow range of mechanical properties of both the membrane and the protein. We show that lipid diffusion is significantly reduced by protein binding at this density regime and even more in areas of high Gaussian curvature, indicating a potential effect on molecular transport in cells. Finally, we reveal that the breaking of the bilayer topology is accompanied by the nematic arrangement of the protein on the surface, a structural motif that likely drives the formation of reticular structures in living cells.

AB - Key cellular processes are frequently accompanied by protein-facilitated shape changes in the plasma membrane. N-BAR-domain protein modules generate curvature by means of complex interactions with the membrane surface. The way they assemble and the mechanism by which they operate are largely dependent on their binding density. Although the mechanism at lower densities has recently begun to emerge, how membrane scaffolds form at high densities remains unclear. By combining electron microscopy and multiscale simulations, we show that N-BAR proteins at high densities can transform a lipid vesicle into a 3D tubular network. We show that this process is a consequence of excess adhesive energy combined with the local stiffening of the membrane, which occurs in a narrow range of mechanical properties of both the membrane and the protein. We show that lipid diffusion is significantly reduced by protein binding at this density regime and even more in areas of high Gaussian curvature, indicating a potential effect on molecular transport in cells. Finally, we reveal that the breaking of the bilayer topology is accompanied by the nematic arrangement of the protein on the surface, a structural motif that likely drives the formation of reticular structures in living cells.

KW - Amino Acid Sequence

KW - Diffusion

KW - Lipid Bilayers

KW - Liposomes

KW - Membrane Proteins

KW - Molecular Dynamics Simulation

KW - Molecular Sequence Data

KW - Protein Binding

KW - Protein Structure, Tertiary

U2 - 10.1016/j.bpj.2013.06.039

DO - 10.1016/j.bpj.2013.06.039

M3 - SCORING: Journal article

C2 - 23931319

VL - 105

SP - 711

EP - 719

JO - BIOPHYS J

JF - BIOPHYS J

SN - 0006-3495

IS - 3

ER -