Why phospholipid molecules form a stable bilayer

Cell Respiration 9. Photosynthesis 3: Genetics 1. Genes 2. Chromosomes 3. Meiosis 4. Inheritance 5. Genetic Modification 4: Ecology 1. Energy Flow 3. Carbon Cycling 4. Climate Change 5: Evolution 1. Evolution Evidence 2. Natural Selection 3. Classification 4. Cladistics 6: Human Physiology 1. Digestion 2. The Blood System 3. Disease Defences 4. Hydrogen bonding and electrostatic attractions ionic bonds occur between the hydrophilic groups of phospholipids and the aqueous solution.

We say that hydrophobic forces cause the bilayer to form, and the other weak forces stabilize the bilayer. This example of one weak force initiating a structural rearrangement that is then stabilized by other weak forces is repeated many times in biology.

Tutorial to help answer the question Placing phospholipids into an aqueous solution immediately results in their forming a lipid bilayer. The phospholipids are very ordered in water, and gain freedom of movement by forming a bilayer.

Water, when associated with lipids, is forced into an ordered arrangement with fewer hydrogen bonds. Forcing lipids into a bilayer gains freedom of movement for the water.

In the gel phase, the Laurdan's dipolar relaxation is produced in the lipidic environment by a few water molecules, showing an emission maximum centered at nm. In the liquid crystalline state, the larger amount of water molecules present in the Laurdan environment induces a relaxation with an emission maximum centered at nm Figure 1.

In figure 1b three regions can be observed. As it has been reported, Laurdan is sensitive to the degree of water penetration into the membrane. GP values above 0. System A presents GP values in the first region around 0. The second region of the same system allows determining the phase transition temperature. Furthermore, the GP values decrease progressively with the increment in DHPC concentration, suggesting that short-chain lipids would induce a decrease in the bilayer packing due to the higher mobility of DHPC present at the lipid surface.

In the first region of system D the GP values are around 0. This indicates that the dynamics of the lipids at the vesicle interface, in both systems, are similar. The temperature range over which the lipid state transition occurs, from gel phase to liquid crystal phase, is broadened.

DPH is a hydrophobic rigid molecule with cylindrical symmetry, solubilized in the acyl chains region of the bilayer. When this probe is excited by polarized light, the dipole emits polarized light in a determined range of angles. Thus, in the gel phase, DPH will have a narrow distribution of angles due to a hindered rotational diffusion. This is observed as high values of fluorescence anisotropy.

In the liquid crystalline phase, DPH will have higher rotational diffusion increasing the angles distribution, and therefore, decreasing the fluorescence anisotropy Figure 2 shows the anisotropy for DPH as a function of temperature for the four systems.

It represents a direct measurement of the order of the bilayer. The increment of DHPC concentration in the lipid mixtures reduces the anisotropy values, indicating that the short-chain lipids diminish the packing of the lipids in the bilayer, increasing the fluidity of the membrane. Interestingly, the systems C and D present a liquid crystalline behavior at lower ranges of temperature. Figure 2. Steady-state fluorescence anisotropy of DPH in the four studied vesicles as a function of temperature.

To obtain detailed information at atomistic level, MD simulations of the four studied systems were performed.

Table 1 shows the number of each species present in every simulation box, representing systems A to D. These numbers correspond to the experimental composition.

Figure 3 on the left shows the top views of the normal to the bilayer surface for systems A to D. The hydrophobic tails are represented in green and the hydrophilic headgroup in blue, respectively. It can be observed that the lipid packing defects are more abundant in the systems with larger concentration of DHPC. To quantify how deep is the penetration of water in the lipid packing defects, we have calculated the accessible solvent area ASA for headgroups and acyl chains of the long-chain lipids in all systems see Table 2.

For ordered systems, as the gel phase, ASA values are expected to be lower because the lipid packing occur in larger extension. The increment in the lipid molecular dynamics increases the bilayer fluidity, inducing larger defects in the lipid packing observed as greater values of ASA From the simulations, we observe that the ASA values increase with increasing DHPC concentration, suggesting that the extension of the acyl chains exposed to the solvent is produced by a higher fluidity of the bilayer.

Figure 3. Snapshot of top view of the four systems at ns of calculation. Atoms in the headgroups and acyl chains are shown in surface representation in blue and green, respectively. Table 2. Additionally, we observe that although DHPC increases the number and size of packing defects in the interfacial region, these defects are not necessarily located along the DHPC molecules, suggesting a global perturbation of the membrane.

Additionally, to evaluate the distance between lipids headgroups in the different leaflets bilayer thickness and the thickness of the interface, the solvent, choline and phosphate group mass distributions are presented for the different lipids in all systems.

These results are shown in Table 2. The increment in the interfacial thickness is explained by the observation that packing defects allow water molecules to penetrate deeper inside the bilayer.

The decrease in bilayer thickness could be explained based on the disorder induced by the DHPC lipids. Considering system A, the density profile for DPPC and SM clearly establishes the division between the two leaflets that compose the bilayer. This division progressively starts to disappear with the increase of DHPC concentration. This observation suggests that the increase of disorder in the bilayer facilitates the interdigitation between the two leaflets, reducing the membrane thickness.

Finally, the interior of lipid bilayer was examined by the calculation of order parameters. System A presents order parameter values typically observed for chain lipids highly ordered like those in gel phases.

The calculated values are near to those reported for DPPC in gel state On the other hand, the values of the order parameter obtained for system D are lower than those obtained for system A, suggesting that chains in system D are less ordered with values typically observed for liquid crystal state.

This behavior is in agreement with previous reports Figure 4. For simplicity, only order parameters for system A and system D are shown. The inclusion of DHPC in the bilayer induces important disorder on the lipid components of the membrane. Low concentration of DHPC induces packing defects over the interfacial and the hydrophobic region. Furthermore, considering that packing defects are not necessarily located near the DHPC molecules, their incorporation suggests a global perturbation of the membrane components.

Finally, increasing the concentration of DHPC induces a liquid crystalline behavior in all the systems studied. The authors are pleased to acknowledge financial support from Fondecyt grant No. Simons, E. Ikonen, Nature , , [ Links ] 2. Simons, J. Sampaio, Cold Spring Harb. Perspect Biol. Brown, E. London, J. Ram, J. Prestegard, Biochim. Acta , , [ Links ] 5. McMahon, J. Gallop, Nature , , [ Links ] 6.

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