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

More documents

Recommendations

Info

$Learning LATEX by Doing$

110 Mesoscopic model for lipid bilayers with embedded proteins φ tilt 60 50 40 30 20 10 N p =4 N p =7 N p =43 0 −15 −10 −5 0 5 10 15 20 25 30 ∆d [Å] Figure 7.5: Protein tilt-angle φ tilt as function of mismatch, ∆d. The data refer to a reduced temperature of T ∗ =0.7 and to the three considered protein sizes NP=4, 7 and 43. The dashed lines are only meant to be a guideline for the eye. Typical configurations of the systems resulting from the simulations are shown on the right. Starting from the top, the snapshots refer to proteins sizes NP=4, 7 and 43. In the three cases the protein hydrophobic length is ˜dP=50 ˚A, hence the hydrophobic mismatch is ∆d=26 ˚A. Theoretical studies based on MD simulations on all-atom models have pointed out the possibility that α-helical hydrophobic peptides may tilt when subjected to positive mismatch conditions [7, 8, 171], the degree of tilting depending on the specific system. The occurrence of protein tilting has also been confirmed experimentally. In fact, the results from very recent experimental investigations by solid state NMR spectroscopy [155] show that α-helical model peptides — of fixed hydrophobic length and with a hydrophobic leucine-alanine core, and tryptophan flanked ends — experience tilt when embedded in phospholipid bilayers of varying hydrophobic thickness (such that dP ≥ do L , i.e. ∆d > 0). It was found that the tilt angle increases by systematically increasing hydrophobic mismatch; however, the tilt dependence on hydrophobic mismatch was not as pronounced as one would have expected, given the degree of mismatch. This result brought the authors to conclude that the tilt of these peptides is energetically unfavorable, and to suggest that the (anchoring) effects by specific residues such as tryptophans are more dominant than mismatch effect. A large tilt is instead experienced by the M13 coat protein peptide when embedded in phospholipid bilayer of varying hydrophobic thickness [154]. For values of mismatch of the same order of the one experienced by the synthetic peptides just
7.3 Results and discussion 111 mentioned [155], the degree of tilting experienced by M13 peptide is much higher. Our simulation data indicate a dependence of the protein-tilt angle on mismatch in agreement with the experimental data just discussed. Incidentally, the results from our simulations suggest that, when a skinny peptide (Np =4) is subjected to a large positive mismatch (dP > do L ), it might bend—besides to experience a tilt—as can be seen by looking at the snapshot shown on the top-right of figure 7.5. Also, as soon as the positive mismatch decreases, the bending disappears, although the peptide still tends to remain tilted. Results from MD simulations on a all-atom model of a poly(32)alanine helical peptide embedded in a dimyristoylphosphatidylcholine (DMPC) bilayer show that this type of helix, not only tilts by 30o as a whole with respect to the bilayer normal, but it also experiences a bend at its middle [7]; MD simulations have also shown a similar tendency for a poly(16)leucine helical peptide embedded in a DMPC bilayer [8]. From the experimental point of view, it is now possible to detect peptide/protein bending by NMR spectroscopy [155,180]. Indeed, the data from Strandberg et al. [155] on the behavior of a synthetic leucine-alanine α-helical peptide in lipid bilayers of varying thickness, do indicate that, for large positive mismatch, the peptides might experience bending (besides tilting), in agreement with our observations. However, we must point out that the occurrence, or extent, of bending of the small peptide (NP=4) might very well be dependent on the value of the bending constant, Kθ, chosen to model the stiffness of the protein chains. 7.3.3 Thermotropic behavior Fluid phase We now discuss the response of the lipid-protein system when the temperature decreases and approaches the main-transition temperature, T ∗ m. The dependence of ξP on the reduced temperature, T ∗ , where T ∗ > T ∗ m, is shown in figure 7.6, for two values of protein hydrophobic length ˜dP=14 ˚A and ˜dP=41 ˚A. These values were chosen to fulfill the condition that either ∆d < 0 or ∆d > 0, respectively, even if by changing temperature the lipid bilayer hydrophobic thickness, and consequently ∆d, may change. The data refer to two protein sizes, NP=7 and 43. The behavior of ξP shown in figure 7.6 indicates that the closer the temperature is to the main-transition temperature, the longer is the perturbation caused by the protein on the surrounding lipids. This is probably due to the enhanced density fluctuations that occur in the pure system close to the transitions temperature. Also, for negative mismatch, there is a pronounced dependence of ξP on the protein size, the larger the protein is, the longer the correlation length becomes. The dependence on protein size can be qualitatively explained by the fact that the larger the protein, the smaller its curvature, and therefore the influence of a given portion of the protein hydrophobic surface extends to more lipids. Although for positive mismatch the dependence on protein size is not that pronounced, the values of ξP in the case of the large protein are systematically
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 18 and 19:
Page 20 and 21:
Page 22 and 23:
Page 24 and 25:
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 39 and 40:
Page 41 and 42:
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 64 and 65:
58 Phase behavior of coarse-grained
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
Page 125 and 126: References [1] Tanford, C. Science
Page 127 and 128: 7.4 Conclusion 121 [68] Ono, S.; Ko
Page 129 and 130: 7.4 Conclusion 123 [139] Lee, A. Bi
Page 131 and 132: Summary Biological membranes, as th
Page 133 and 134: agreement we find gives us confiden
Page 135 and 136: Samenvatting Biologische membranen,
Page 137 and 138: de lage temperatuur gel fase of Lβ
Page 139: ied dat het dichtst bij het hydrofo
Page 143: This thesis is based on the followi
show all

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

Create successful ePaper yourself

Delete template?

Save as template?