Mesoscopic models of lipid bilayers and bilayers with embedded ...
Mesoscopic models of lipid bilayers and bilayers with embedded ... Mesoscopic models of lipid bilayers and bilayers with embedded ...
82 Interaction of small molecules with bilayers t t t t ht7 t t t t (L) t (L) t (L) t (L) t (L) t (L) t ht 6t (L) t (L) t (K) t (K) t (L) t (K) t (K) h t 4 (K) t (L) t (L) Figure 6.1: Schematic representation of the three lipid types used in this study with their nomenclature. 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, and type, 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 in a bond-bending potential with θo = 135 o , while a bead labeled as ’t’ does not participate to any bond-bending potential. The subscript indicates the number of beads of a given type that are tied together. 6.3 Results and Discussion 6.3.1 Partitioning of the solutes in the bilayer Figure 6.2 shows the snapshots of the equilibrium configuration of the dbA, dbH and dbN molecules in the poly-unsaturated bilayer. The distributions of the solutes in the other bilayer types are similar to the ones shown here. The partitioning at equilibrium of the solutes molecules depends on the chemical interactions with the bilayer components and with water: the amphiphilic molecules are found near the lipid headgroup (figure 6.2(a)) while the hydrophobic molecules are located in the bilayer core (figure 6.2(b)). Only the neutral molecules (figure 6.2(c)) have significantly diffused into the water phase. As a general observation, we see that the dumbbells have higher density in the energetically more favorable bilayer region, i.e. where the repulsion is lower. However, the neutral molecules that have not diffused in the water, are found predominantly near the lipid headgroup region (figure 6.2(c)). Because of their neutrality, the preference for these molecules to absorb at the interface must be due to thermodynamic factors, like density and pressure distributions t t
6.3 Results and Discussion 83 within the bilayer. The neutral dumb-bells locate in fact in the bilayer region with the lowest density and pressure, which corresponds to the interface between the hydrophilic headgroups and the hydrophobic tails of the lipids. These observations are supported by the shape of the density profiles as shown in figures 6.3, 6.4, and 6.5. Considering the interaction energy only, purely hydrophobic dumb-bells should be found with uniform distribution within the bilayer core. However, when we compare the location of the hydrophobic dumb-bells with the shape of the lateral pressure within the pure bilayer (also shown in the figures), we observe that the distribution of the solute molecules is not uniform, but follows the distribution of the lipid density and pressure within the bilayer core. The hydrophobic dumb-bells locate in the regions of lower hydrocarbon density and pressure. These observations suggest that the distributions of density and pressure in the bilayer is an important factor in predicting the absorption sites for small solute molecules. 6.3.2 Effect on the bilayer properties By comparing the density profiles in presence of solutes with the ones for the pure bilayer, we can study how the bilayer structure is modified by the addition of these molecules. As shown in Chapter 4, for stiff lipids with the headgroup repulsion parameter used here, the structure of the pure system is a largely interdigitated bilayer. If the dumb-bells are located at the interface (amphiphilic and neutral) in this kind of bilayer (figures 6.3(c) and 6.3(d)) the central density peak in the bilayer hydrophobic core increases in magnitude, while the secondary peaks at the edge of the hydrophobic core decrease in magnitude. Both these features in the density profile are a signature for an increase in interdigitation. The opposite happens when hydrophobic dumb-bells are added (figure 6.3(b)). Since these molecules adsorb in the bilayer hydrophobic core, they decrease the packing of the lipid tails and increase their disorder. As a consequence, the bilayer is less interdigitated; the peaks in the density of the last bead of the tail shift toward the bilayer center, and the overall density in the bilayer core becomes more uniform. For the flexible and the unsaturated bilayers (figures 6.5 and 6.4), the addition of solutes has a smaller effect on the lipids density distribution. A general observation for both the flexible and the unsaturated bilayer is that the addition of hydrophobic molecules decreases the central minimum (at z = 0) of the lipid tail density. This effect can be easily explained considering that the hydrophobic dumb-bells adsorb in the bilayer inner core, and hence decrease the space available to the lipid tails in this region. To further characterize the modifications induced by the solute molecules on the bilayer, we compare the structural quantities of the mixed bilayer with the ones of
- Page 37 and 38: 3.4 Surface tension in lipid bilaye
- Page 39 and 40: 3.4 Surface tension in lipid bilaye
- Page 41 and 42: 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 64 and 65: 58 Phase behavior of coarse-grained
- Page 66 and 67: 60 Phase behavior of coarse-grained
- Page 68 and 69: 62 Phase behavior of coarse-grained
- Page 70 and 71: 64 Phase behavior of coarse-grained
- Page 72 and 73: 66 Phase behavior of coarse-grained
- Page 74 and 75: 68 Phase behavior of coarse-grained
- Page 76 and 77: 70 Phase behavior of coarse-grained
- Page 78 and 79: 72 Phase behavior of coarse-grained
- Page 80 and 81: 74 Phase behavior of coarse-grained
- Page 82 and 83: 76 Phase behavior of coarse-grained
- Page 85 and 86: VI Interaction of small molecules w
- Page 87: 6.2 Computational details 81 For re
- 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 108 and 109: 102 Mesoscopic model for lipid bila
- Page 110 and 111: 104 Mesoscopic model for lipid bila
- Page 112 and 113: 106 Mesoscopic model for lipid bila
- Page 114 and 115: 108 Mesoscopic model for lipid bila
- Page 116 and 117: 110 Mesoscopic model for lipid bila
- Page 118 and 119: 112 Mesoscopic model for lipid bila
- Page 120 and 121: 114 Mesoscopic model for lipid bila
- Page 122 and 123: 116 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
82 Interaction <strong>of</strong> small molecules <strong>with</strong> <strong>bilayers</strong><br />
t<br />
t<br />
t<br />
t<br />
ht7<br />
t<br />
t<br />
t<br />
t (L)<br />
t (L)<br />
t (L)<br />
t (L)<br />
t (L)<br />
t (L)<br />
t<br />
ht 6t<br />
(L)<br />
t (L)<br />
t (K)<br />
t (K)<br />
t (L)<br />
t (K)<br />
t (K)<br />
h t 4<br />
(K)<br />
t (L)<br />
t (L)<br />
Figure 6.1: Schematic representation <strong>of</strong> the three <strong>lipid</strong> types used in this study <strong>with</strong> their<br />
nomenclature. The head-bead is represented by a black particle <strong>and</strong> is denoted as ’h’. The<br />
tail-beads are represented by white particles <strong>and</strong> have different names depending on the presence,<br />
<strong>and</strong> type, <strong>of</strong> a bond-bending potential. A bead labeled ’t (L) ’ is the central bead in a<br />
bond-bending potential <strong>with</strong> equilibrium angle θo = 180 o , a bead labeled ’t (K) ’ is the central<br />
bead in a bond-bending potential <strong>with</strong> θo = 135 o , while a bead labeled as ’t’ does not participate<br />
to any bond-bending potential. The subscript indicates the number <strong>of</strong> beads <strong>of</strong> a given<br />
type that are tied together.<br />
6.3 Results <strong>and</strong> Discussion<br />
6.3.1 Partitioning <strong>of</strong> the solutes in the bilayer<br />
Figure 6.2 shows the snapshots <strong>of</strong> the equilibrium configuration <strong>of</strong> the dbA, dbH <strong>and</strong><br />
dbN molecules in the poly-unsaturated bilayer. The distributions <strong>of</strong> the solutes in<br />
the other bilayer types are similar to the ones shown here. The partitioning at equilibrium<br />
<strong>of</strong> the solutes molecules depends on the chemical interactions <strong>with</strong> the bilayer<br />
components <strong>and</strong> <strong>with</strong> water: the amphiphilic molecules are found near the<br />
<strong>lipid</strong> headgroup (figure 6.2(a)) while the hydrophobic molecules are located in the<br />
bilayer core (figure 6.2(b)). Only the neutral molecules (figure 6.2(c)) have significantly<br />
diffused into the water phase. As a general observation, we see that the dumbbells<br />
have higher density in the energetically more favorable bilayer region, i.e. where<br />
the repulsion is lower. However, the neutral molecules that have not diffused in the<br />
water, are found predominantly near the <strong>lipid</strong> headgroup region (figure 6.2(c)). Because<br />
<strong>of</strong> their neutrality, the preference for these molecules to absorb at the interface<br />
must be due to thermodynamic factors, like density <strong>and</strong> pressure distributions<br />
t<br />
t
Change language