Mesoscopic models of lipid bilayers and bilayers with embedded ...

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42 Structural characterization of lipid bilayers were first self-assembled from an initial random configuration of the lipids in water. The self-assembly of the bilayers required approximately 10000 DPD steps with a timestep of ∆t = 0.03. To obtain the reference state of zero surface tension, 50000 hybrid MC-DPD cycles were performed with imposed surface tension γ = 0. The bilayer remained the stable state throughout the equilibration run. After equilibration, structural quantities were computed over 50000 hybrid MC-DPD cycles, with γ = 0. To illustrate the lipid nomenclature we will use in the text respect to the tail stiffness, we consider two consecutive bonds in the lipid tails, i.e. the bonds between beads i − 1, i and i, i + 1. If no bond-bending potential is defined between the bond vectors, bead i will be called t, if a bond-bending potential is defined with equilibrium angle θo = 180 o , bead i will be called t (L) , and if the equilibrium angle is set to θo = 135 o (corresponding to a point of cis-unsaturation) bead i will be called t (K) . Figure 4.1 gives an illustration of this nomenclature. t t (K) 135 o t t (L) t 180 o Figure 4.1: Schematic representation to illustrate the nomenclature for the lipid beads used in the text. The head bead is represented by a black particle and is denoted as ’h’. The tail beads are represented by white particles and have different names depending on the presence of a bond-bending potential. A bead labeled ’t (L) ’ is the central bead in a bond-bending potential with equilibrium angle θo = 180 o , a bead labeled ’t (K) ’ is the central bead for a bond-bending potential with θo = 135 o , while a bead labeled as ’t’ does not participate to any bond-bending potential. 4.4 Results and discussion 4.4.1 Density profiles We first consider single-tail lipids with chain length of five beads, and study the differences in the bilayer structure between a fully flexible lipid, denoted as ht5, and a stiff one, denoted as ht (L) 4 t. Both these lipids self-assemble in a stable bilayer phase, the internal organization of the bilayer, however, strongly depends on the lipid architecture, as shown in figure 4.2. Some general features of the density distribution, such as the lipid tails confined in the inner hydrophobic core and the higher density at the interfacial region, where headgroups and water pack tightly, are in good qualitative agreement with the packing of a phospholipid bilayer. No water permeation in the bilayer core is observed and a partial overlap of the headgroup with the first
4.4 Results and discussion 43 ρ(z) 3 2 1 0 −6 −4 −2 0 Z 2 4 6 (a) ht5 w h t (1,..,n−1) t n ρ tot ρ(z) 3 2 1 0 −6 −4 −2 0 Z 2 4 6 (b) ht (L) 4 t w h t (1,..,n−1) t n ρ tot Figure 4.2: Density profiles across the bilayer as function of the distance from the bilayer center (z = 0) for two single-tail lipid models: (a) flexible and (b) stiff. The density distribution is shown for water (w, thin solid black line); headgroups (h, thick solid black line); terminal tail bead tn (thick dot-dashed black line); and the remaining tail beads t1,..n−1 (thick dashed black line). The total density ρtot (thick solid gray line) is also shown. segments of the lipid tails is present. These observations are in agreement with MD simulations of hydrated phospholipid bilayers [63, 77, 87, 88]. The typical electron density profiles in lipid bilayers measured experimentally [78,85], or calculated in atomistic MD simulations [62,89] show a distinct lower density in the bilayer center compared with the tightly packed region in the vicinity of the headgroup. Given the coarse-grained nature of our model, and the soft interactions between the beads, we find a larger overlap of the lipids in the bilayer inner core compared with experimental and MD results. This overlap has different causes depending on the lipid type. Although always located in the bilayer core, the tail beads have very different distributions in the two bilayers corresponding to the different lipids. In the bilayer formed by the flexible lipids, the maximum density for the terminal tail bead is in the center of the bilayer, and the total density presents a small dip in the bilayer center. This indicates that the two monolayers are not very interdigitated. The distribution of the terminal tail-beads, however, shows that the lipids in the bilayer are very disordered. The lipids can curl, and the terminal tail beads have a non negligible probability to be found near the headgroup region of the monolayer to which they belong. It should be expected that stiff lipids, for which there is an energy barrier to the disordering of the tails, would be more localized. However, as it can be clearly seen from figure 4.2(b), the bilayer of stiff lipids has a completely different structure in the hydrophobic core compared to the bilayer of flexible lipids. The terminal tail beads are not located in the midplane region but rather close to the headgroups of the opposing monolayer, and their density distri-
Page 1: Mesoscopic models of lipid bilayers
Page 4 and 5: Promotiecommissie: Promotor: • pr
Page 6 and 7: ii CONTENTS 5.3 Double-tail lipid b
Page 8 and 9: 2 Introduction 1.1 The cell membran
Page 10 and 11: 4 Introduction between the beads, a
Page 12 and 13: 6 Introduction whether the preferre
Page 14 and 15: 8 Simulation method for coarse-grai
Page 16 and 17: 10 Simulation method for coarse-gra
Page 27 and 28: III Surface tension in lipid bilaye
Page 29 and 30: 3.2 Method of calculation of surfac
Page 31 and 32: 3.2 Method of calculation of surfac
Page 33 and 34: 3.3 Constant surface tension ensemb
Page 35 and 36: 3.3 Constant surface tension ensemb
Page 37 and 38: 3.4 Surface tension in lipid bilaye
Page 43 and 44: IV Structural characterization of l
Page 45 and 46: 4.2 Structural quantities 39 been r
Page 47: 4.3 Computational details 41 lipid
Page 51 and 52: 4.4 Results and discussion 45 one l
Page 53 and 54: 4.4 Results and discussion 47 WH HT
Page 55 and 56: 4.4 Results and discussion 49 Shill
Page 57 and 58: 4.4 Results and discussion 51 chain
Page 59 and 60: 4.4 Results and discussion 53 4.4.4
Page 61: 4.4 Results and discussion 55 headg
Page 64 and 65: 58 Phase behavior of coarse-grained
Page 85 and 86: VI Interaction of small molecules w
Page 87 and 88: 6.2 Computational details 81 For re
Page 89 and 90: 6.3 Results and Discussion 83 withi
Page 91 and 92: 6.3 Results and Discussion 85 ρ(z)
Page 93 and 94: 6.3 Results and Discussion 87 ρ(z)
Page 95 and 96: 6.3 Results and Discussion 89 S m 0
Page 97 and 98: 6.3 Results and Discussion 91 π(z)
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6.3 Results and Discussion 93 the l
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96 Mesoscopic model for lipid bilay
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98 Mesoscopic model for lipid bilay
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100 Mesoscopic model for lipid bila
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References [1] Tanford, C. Science
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7.4 Conclusion 121 [68] Ono, S.; Ko
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7.4 Conclusion 123 [139] Lee, A. Bi
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Summary Biological membranes, as th
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agreement we find gives us confiden
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Samenvatting Biologische membranen,
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de lage temperatuur gel fase of Lβ
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ied dat het dichtst bij het hydrofo
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This thesis is based on the followi
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