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 ...
114 Mesoscopic model for lipid bilayers with embedded proteins lipid-ordered region, there appears a few-layer thick region (which for convenience we denote ‘undershooting’ region) where the bilayer has an hydrophobic thickness that is less that the one in the bulk. This undershooting phenomenon is probably due to the fact that, on the one hand, the system has to satisfy the boundary-constraint imposed by the value of the hydrophobic bilayer thickness of the bulk; and, on the other hand, the system has to adjust to the perturbation caused by the protein in such a way to hold the bilayer density constant, also close to the protein. We suggest that, if the protein is large enough that tilting is unfavorable, and if the mismatch is large enough that even the ordered (gel-like) lipids closest to the protein are not able to match its hydrophobic surface, a void is formed in the center of the bilayer. To fill this void and maintain the constraint of uniform density in the bilayer core, the lipid chains in the ‘undershooting’ region might tilt and bend toward the protein. This hypothesis is indeed consistent with the fact that, although the end-to-end distance of the lipids in the undershooting region is approximately equal to the one of the lipids in the bulk, the projected length on the bilayer normal is shorter than the one of the lipids in the bulk. Therefore, in the undershooting region, the bilayer hydrophobic thickness is smaller than in the bulk. In the case of dP < do L (see figure 7.7a), the bilayer in a neighboring region (which in this case we call ‘overshooting’ region) to the one closest to the protein interface has an hydrophobic thickness that is higher than the one of the lipid bilayer in the bulk. This might be explained by the fact that the lipid chains nearest to the protein might tilt (and possibly bend) to satisfy the matching constraint. At the same time the lipids in the ‘overshooting’ region stretch their chains (i.e. become more gel-like) to satisfy the constant-density constraint. This is consistent with the fact that, in the region closest to the protein (the so-called ‘annulus’), the values of the order parameter of the lipid chains, and of both the lipid end-to-end distance and projected length, are smaller than the values in the bulk. This shows that the lipids closest to the protein are more disordered and might bend to match the protein hydrophobic length (which is shorter than the bilayer thickness at the considered temperature). On the other hand, the projected length on the bilayer normal of the lipids in the overshooting region is slightly longer than the one of the lipids in the bulk; also the order parameter, S, in the overshooting region is higher than in the bulk. This indicates that the lipids in this region are more stretched and ordered (i.e. gel-like) than the lipids in the bulk. Finally, we want to point out that the overshooting/undershooting effect seems not to be due to finite-size effects. There could be a number of interesting biological implications if a curved structure resulting from the overshooting/undershooting effect occurs around proteins embedded in biological membranes. Its presence could affect the permeability properties of the membrane in the vicinity of each protein; it could be a basis for lipidsorting in the vicinity of the protein and when more than one lipid species is present in the system; it could also be a way to regulate protein-protein contacts, hence pro-
7.3 Results and discussion 115 tein lateral distribution; finally, it could create a fertile (or adverse) ground for the attachment of fusion peptides, which are known to enter the bilayer in a oblique manner [185,186], and thus could be favored by the presence of tilted lipids. It could also cause a change in the lateral pressure profile around each protein, which in turn could induce conformational changes in the proteins. Furthermore, if there exists an overshooting/undershooting effect, one should be careful in the interpretation of results obtained from spectroscopic measurements of the lipid order parameter S; if the protein concentration is high enough that there is a sufficient number of overshooting/undershooting lipids around the isolated proteins, calculation of the lipid bilayer hydrophobic thickness from measurements of S could give underestimation/overestimation of the value of the hydrophobic thickness. Gel phase Finally, we discuss the behavior of the lipid-protein system below the melting temperature, i.e. in the gel phase. The results from the simulations are illustrated in two figures. Figure 7.8 shows the snapshots of two typical configurations obtained from the simulation of bilayers with embedded a NP=43 protein. The simulations are done (a) ∆d > 0 (b) ∆d < 0 Figure 7.8: Snapshots of two typical configurations of lipid-protein bilayers at a reduced tem- perature T ∗ =0.25, corresponding to the Lβ ′ or gel-phase. The calculated value of the pure lipid bilayer thickness is d o L =(36.6±0.1) ˚A. In (a) is shown the case of a protein of size NP=43 and ˜dP=50 ˚A, thus subjected to a positive mismatch ∆d=13 ˚A, while in (b) is shown the case of a NP=43 size protein, but with ˜dP=14 ˚A, thus subjected to negative mismatch ∆d=-23 ˚A. at a reduced temperature T∗ =0.25, corresponding to the Lβ ′ or gel-phase. The pure lipid bilayer in the Lβ ′ is characterized by a tilted orientation of the lipids, as previously discussed. The calculated value of the pure lipid bilayer thickness at this reduced temperature is do L =(36.6±0.1) ˚A. In figure 7.8(a) is shown the case of a protein with ˜dP=50 ˚A, thus subjected to a positive mismatch ∆d=13 ˚A. The response of the protein to the positive mismatch is to tilt slightly to decrease its effective length, and thus orient parallel to the tilted lipids in the gel-state.
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- Page 85 and 86: VI Interaction of small molecules w
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- 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
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7.3 Results <strong>and</strong> discussion 115<br />
tein lateral distribution; finally, it could create a fertile (or adverse) ground for the<br />
attachment <strong>of</strong> fusion peptides, which are known to enter the bilayer in a oblique<br />
manner [185,186], <strong>and</strong> thus could be favored by the presence <strong>of</strong> tilted <strong>lipid</strong>s. It could<br />
also cause a change in the lateral pressure pr<strong>of</strong>ile around each protein, which in turn<br />
could induce conformational changes in the proteins. Furthermore, if there exists<br />
an overshooting/undershooting effect, one should be careful in the interpretation<br />
<strong>of</strong> results obtained from spectroscopic measurements <strong>of</strong> the <strong>lipid</strong> order parameter<br />
S; if the protein concentration is high enough that there is a sufficient number <strong>of</strong><br />
overshooting/undershooting <strong>lipid</strong>s around the isolated proteins, calculation <strong>of</strong> the<br />
<strong>lipid</strong> bilayer hydrophobic thickness from measurements <strong>of</strong> S could give underestimation/overestimation<br />
<strong>of</strong> the value <strong>of</strong> the hydrophobic thickness.<br />
Gel phase<br />
Finally, we discuss the behavior <strong>of</strong> the <strong>lipid</strong>-protein system below the melting temperature,<br />
i.e. in the gel phase. The results from the simulations are illustrated in two<br />
figures. Figure 7.8 shows the snapshots <strong>of</strong> two typical configurations obtained from<br />
the simulation <strong>of</strong> <strong>bilayers</strong> <strong>with</strong> <strong>embedded</strong> a NP=43 protein. The simulations are done<br />
(a) ∆d > 0 (b) ∆d < 0<br />
Figure 7.8: Snapshots <strong>of</strong> two typical configurations <strong>of</strong> <strong>lipid</strong>-protein <strong>bilayers</strong> at a reduced tem-<br />
perature T ∗ =0.25, corresponding to the Lβ ′ or gel-phase. The calculated value <strong>of</strong> the pure <strong>lipid</strong><br />
bilayer thickness is d o L =(36.6±0.1) ˚A. In (a) is shown the case <strong>of</strong> a protein <strong>of</strong> size NP=43 <strong>and</strong><br />
˜dP=50 ˚A, thus subjected to a positive mismatch ∆d=13 ˚A, while in (b) is shown the case <strong>of</strong> a<br />
NP=43 size protein, but <strong>with</strong> ˜dP=14 ˚A, thus subjected to negative mismatch ∆d=-23 ˚A.<br />
at a reduced temperature T∗ =0.25, corresponding to the Lβ ′ or gel-phase. The pure<br />
<strong>lipid</strong> bilayer in the Lβ ′ is characterized by a tilted orientation <strong>of</strong> the <strong>lipid</strong>s, as previously<br />
discussed. The calculated value <strong>of</strong> the pure <strong>lipid</strong> bilayer thickness at this reduced<br />
temperature is do L =(36.6±0.1) ˚A. In figure 7.8(a) is shown the case <strong>of</strong> a protein<br />
<strong>with</strong> ˜dP=50 ˚A, thus subjected to a positive mismatch ∆d=13 ˚A. The response <strong>of</strong> the<br />
protein to the positive mismatch is to tilt slightly to decrease its effective length, <strong>and</strong><br />
thus orient parallel to the tilted <strong>lipid</strong>s in the gel-state.
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