Mechanical properties of lipid bilayers from molecular dynamics simulation

Venable, Richard M.; Brown, Frank L. H.; Pastor, Richard W.

doi:10.1016/j.chemphyslip.2015.07.014

Cited by 270 publications

(423 citation statements)

References 88 publications

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“…1B). The energetic cost of the deformation, using standard material properties of 1-palmitoyl-2-oleoyl PC (POPC) bilayers (Table S1) (17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27), is 60 kcal/mol, and the bending energy dominates over the compression and surface tension terms.…”

Section: Tmem16 Induces Large-scale Membrane Deformationsmentioning

confidence: 99%

Atomistic insight into lipid translocation by a TMEM16 scramblase

Bethel

Grabe

2016

Proc. Natl. Acad. Sci. U.S.A.

101

159

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The transmembrane protein 16 (TMEM16) family of membrane proteins includes both lipid scramblases and ion channels involved in olfaction, nociception, and blood coagulation. The crystal structure of the fungal Nectria haematococca TMEM16 (nhTMEM16) scramblase suggested a putative mechanism of lipid transport, whereby polar and charged lipid headgroups move through the low-dielectric environment of the membrane by traversing a hydrophilic groove on the membrane-spanning surface of the protein. Here, we use computational methods to explore the membrane-protein interactions involved in lipid scrambling. Fast, continuum membrane-bending calculations reveal a global pattern of charged and hydrophobic surface residues that bends the membrane in a large-amplitude sinusoidal wave, resulting in bilayer thinning across the hydrophilic groove. Atomic simulations uncover two lipid headgroup-interaction sites flanking the groove. The cytoplasmic site nucleates headgroup-dipole stacking interactions that form a chain of lipid molecules that penetrate into the groove. In two instances, a cytoplasmic lipid interdigitates into this chain, crosses the bilayer, and enters the extracellular leaflet, and the reverse process happens twice as well. Continuum membrane-bending analysis carried out on homology models of mammalian homologs shows that these family members also bend the membrane-even those that lack scramblase activity. Sequence alignments show that the lipid-interaction sites are conserved in many family members but less so in those with reduced scrambling ability. Our analysis provides insight into how large-scale membrane bending and protein chemistry facilitate lipid permeation in the TMEM16 family, and we hypothesize that membrane interactions also affect ion permeation.TMEM16 | lipid scrambling | continuum membrane models | simulation | anoctamin T he compositional asymmetry between the leaflets of the plasma membrane influences the signaling properties of cells. Scramblases are a class of proteins that disrupt membrane asymmetry by facilitating the transfer of phospholipids from one leaflet to the other in an energy-independent manner. These transmembrane proteins play a role in events such as coagulation of the blood and cellular apoptosis by transporting phosphatidylserine (PS) from the inner leaflet to the outer leaflet of the plasma membrane (1). In particular, transmembrane protein 16 (TMEM16) family members have gained recent attention for their role in phospholipid scrambling in platelets and fungi. The TMEM16 family members have diverse functions. For example, TMEM16A and -B are calcium-activated chloride channels, TMEM16F is a nonspecific cation channel and scramblase, and the fungal Aspergillus fumigatus TMEM16 is another dual scramblase/ion channel (2-6).The structure of the Nectria haematococca TMEM16 (nhTMEM16) membrane protein revealed a possible mechanism for phospholipid conduction across the membrane (Fig. 1A) (7). The protein forms a dimer, and each subunit has a hydrophilic groove composed of polar...

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Section: Tmem16 Induces Large-scale Membrane Deformationsmentioning

confidence: 99%

Atomistic insight into lipid translocation by a TMEM16 scramblase

Bethel

Grabe

2016

Proc. Natl. Acad. Sci. U.S.A.

101

159

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“…Oleic acids are unsaturated with a cis double bond between carbons 9 and 10 in the tail; this introduces packing disorder in bilayers. Palmitic acids are fully saturated and pure DPPC bilayers are relatively more ordered than those with unsaturated chains [6]. POPC molecules contain one oleic and one palmitic acid, and is the more common lipid in biological membranes.…”

Section: Introductionmentioning

confidence: 99%

“…DOPC, DPPC, and POPC ( Fig. 1) are selected, because these membranes have a different degree of ordering as is observed in the structure factors [6,7]. This study is therefore a precursor to studying liquid (dis)ordered phases (Lo and Ld) [8], which are models of membrane rafts.…”

Section: Introductionmentioning

confidence: 99%

Oxygen Transport to Tissue XL

2018

Advances in Experimental Medicine and Biology

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Rafts are nanoscale ordered domains in biological membranes that are rich in saturated phospholipids. In this study, the influence of chain unsaturation and temperature on oxygen diffusion through lipid membranes is examined using advanced computational modeling. The studied phospholipids with increasing unsaturation are: 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), and 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC). The unsaturation correlates with the area per lipid and the order parameter. Oxygen diffusion is found to be faster at higher temperature, and the solubility of oxygen in the membrane with respect to water decreases. Diffusion varies over a larger range across the membrane at 323 K in DPPC than in DOPC, whereas POPC has intermediate diffusivity. Oxygen diffusion in saturated lipids is faster at the membrane center and slower near the head group region than in unsaturated lipids. Oxygen solubility in DPPC is higher than in unsaturated lipids.

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“…Equation (21) clearly shows that σ bend xx (z) is a linear function of λ for z 1 < z < z 3 . Our simulation results indicate that this linear relation is approximately satisfied even when averaging the conformations in whichr bv are fluctuated around the xy plane.…”

Section: Lateral Pressure Profilementioning

confidence: 99%

“…Two opposing forces, interfacial tension and steric repulsion, produce the inhomogeneous stress inside the bilayers [19]. This inhomogeneity is a key property of the bilayers because it determines the area per lipid molecule [19], spontaneous curvature [20][21][22][23][24], Gaussian curvature modulus [21][22][23][24][25][26][27][28], and function of the mechanosensitive channel [29,30]. Since the stress profile cannot be obtained experimentally [31,32], estimation using molecular simulations is important.…”

Section: Introductionmentioning

confidence: 99%

Nonuniqueness of local stress of three-body potentials in molecular simulations

Nakagawa

Noguchi

2016

Phys. Rev. E

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Microscopic stress fields are widely used in molecular simulations to understand mechanical behavior. Recently, decomposition methods of multibody forces to central force pairs between the interacting particles have been proposed. Here, we introduce a force center of a three-body potential and propose different force decompositions that also satisfy the conservation of translational and angular momentum. We compare the force decompositions by stress-distribution magnitude and discuss their difference in the stress profile of a bilayer membrane using coarse-grained and atomistic molecular dynamics simulations.

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Mechanical properties of lipid bilayers from molecular dynamics simulation

Cited by 270 publications

References 88 publications

Atomistic insight into lipid translocation by a TMEM16 scramblase

Atomistic insight into lipid translocation by a TMEM16 scramblase

Oxygen Transport to Tissue XL

Nonuniqueness of local stress of three-body potentials in molecular simulations

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