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

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58 Phase behavior of coarse-grained lipid bilayers 5.1 Introduction As we have discussed in the previous Chapter, an important question in the development of a mesoscopic model is how much chemical detail should be included in the model. We have described in some detail the structural characteristics of bilayers of single-tail lipids. In this Chapter, we investigate if such a model correctly describes the (phase) behavior of double tail phospholipids, and we compare the results of our simulations with experiments that are performed on single-tail lipids. In the second part of this Chapter we increase the complexity of the model lipids, by studying the phase behavior of a double-tail lipid with three hydrophilic headbeads and five hydrophobic beads in each of the tails. Furthermore, we show that a correspondence can be made between reduced and physical temperature. With this mapping, and the mapping of reduced length scales onto physical lengths, the typical bilayer characteristics, like the area per lipid and bilayer thickness, computed in the simulations are found to be in good quantitative agreement with experimental results. In particular, we show that this lipid model correctly reproduces the phase behavior of dimyristoylphosphatidylcholine (DMPC) lipid bilayers. The phase behavior of different phosphocholines (PC’s) has been determined experimentally (see [96] for a review). All PC’s have a low temperature Lβ ′ phase (see figure 5.1(a)). In this phase the bilayer is a gel: the chains of the phospholipids are ordered and show a tilt relative to the bilayer normal. At higher temperature the Lα phase is the stable phase. This phase is the liquid crystalline state of the bilayer in which the chains are disordered and tail overlap due to this thermal disorder is possible. This phase is physiologically the most relevant [97]. (a) L β ′ (b) P β ′ (c) Lα (d) LβI Figure 5.1: Schematic drawings of the various bilayer phases. The characteristics of these phases are explained in the text. The filled circles represent the hydrophilic headgroup of a phospholipid and the lines represent the hydrophobic tails. Under normal conditions the two monolayers of a bilayer contact each other at the terminal methyl group of their hydrophobic chains, while their hydrophilic headgroups are in contact with water. However, it is known experimentally that at low temperatures an interdigitated state, in which the terminal methyl groups of one monolayer interpenetrate the opposing layer, is also possible. This LβI phase
5.2 Single-tail lipid bilayers 59 does not spontaneously form in bilayers of symmetrical chain phospholipids, like dipalmitoylphosphatidylcholines (DPPC), [98] but can be induced by changes in the environment, like hydrostatic pressure or changes in the pH of the solution [99], or by incorporation, at the membrane interface of small amphiphilic molecules, like alcohols [90, 100, 101], or anesthetics [102]. Interdigitation can also be induced by changes in the lipid structure, for example by introducing an ester-linkage in the headgroup of the phospholipids [103, 104]. Interdigitation reduces the bilayer thickness, and this can, for example, affect the diffusion of ions across the bilayer or influence the activity of membrane proteins. It has been proposed [91, 99] that specific interactions are not important in the formation of an interdigitated phase, and that the main driving force that induces interdigitation is an increase in the headgroup surface area, which results in the creation of voids between the molecules. Since voids in the bilayer core are energetically unfavorable, they are filled up by molecules of the opposite monolayer. This mechanism suggests that the formation of an interdigitated phase should be a general phenomenon. This would imply that an interdigitated phase could also be induced in bilayers of, for example, single-tail lipids. The fact that for single-tail lipids the interdigitated phase has not been observed experimentally, is one of the motivations to investigate the molecular aspects underlying the formation of an interdigitated phase in more detail. Our simulations correctly describe the hydrophobic tail length dependence of this transition and the effect of adding salt. In addition, the simulations predict that both the interdigitated and non-interdigitated phases can be formed in systems with single-tail lipids. Conversely, we do not find any spontaneous interdigitation is bilayers of double-tail lipids. 5.2 Single-tail lipid bilayers 5.2.1 Computational details In this investigation we consider lipids with one head segment connected to a single tail with variable length (see figure 5.2). Two consecutive beads are connected by harmonic springs with spring constant Kr = 100 and ro = 0.7. A harmonic bond bending potential between three consecutive beads is added with a bending constant Kθ = 10 and an equilibrium angle θ0 = 180 ◦ .
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Mesoscopic models of lipid bilayers
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Promotiecommissie: Promotor: • pr
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ii CONTENTS 5.3 Double-tail lipid b
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2 Introduction 1.1 The cell membran
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4 Introduction between the beads, a
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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 and 48: 4.3 Computational details 41 lipid
Page 49 and 50: 4.4 Results and discussion 43 ρ(z)
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 66 and 67: 60 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)
Page 99: 6.3 Results and Discussion 93 the l
Page 102 and 103: 96 Mesoscopic model for lipid bilay
Page 104 and 105: 98 Mesoscopic model for lipid bilay
Page 106 and 107: 100 Mesoscopic model for lipid bila
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108 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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