Some lipid tails consist of saturated fatty acids and some contain unsaturated fatty acids. This combination adds to the fluidity of the tails that are constantly in motion. The cell membrane consists of two adjacent layers of phospholipids, which form a bilayer. The fatty acid tails of phospholipids face inside, away from water, whereas the phosphate heads face the outward aqueous side. Since the heads face outward, one layer is exposed to the interior of the cell and one layer is exposed to the exterior.
As the phosphate groups are polar and hydrophilic, they are attracted to water in the intracellular fluid. Phospholipid Bilayer : The phospholipid bilayer consists of two adjacent sheets of phospholipids, arranged tail to tail. The hydrophobic tails associate with one another, forming the interior of the membrane. The polar heads contact the fluid inside and outside of the cell. As a result, there are two distinct aqueous compartments on each side of the membrane. This separation is essential for many biological functions, including cell communication and metabolism.
Biological membranes remain fluid because of the unsaturated hydrophobic tails, which prevent phospholipid molecules from packing together and forming a solid. If a drop of phospholipids is placed in water, the phospholipids spontaneously form a structure known as a micelle, with their hydrophilic heads oriented toward the water. Micelles are lipid molecules that arrange themselves in a spherical form in aqueous solution.
The formation of a micelle is a response to the amphipathic nature of fatty acids, meaning that they contain both hydrophilic and hydrophobic regions.
Steroids, like cholesterol, play roles in reproduction, absorption, metabolism regulation, and brain activity. Unlike phospholipids and fats, steroids have a fused ring structure. Although they do not resemble the other lipids, they are grouped with them because they are also hydrophobic and insoluble in water.
All steroids have four linked carbon rings, and many of them, like cholesterol, have a short tail. Many steroids also have the —OH functional group, and these steroids are classified as alcohols called sterols. Steroid Structures : Steroids, such as cholesterol and cortisol, are composed of four fused hydrocarbon rings. Cholesterol is the most common steroid and is mainly synthesized in the liver; it is the precursor to vitamin D. Cholesterol is also a precursor to many important steroid hormones like estrogen, testosterone, and progesterone, which are secreted by the gonads and endocrine glands.
Cholesterol also plays a role in synthesizing the steroid hormones aldosterone, which is used for osmoregulation, and cortisol, which plays a role in metabolism. Cholesterol is also the precursor to bile salts, which help in the emulsification of fats and their absorption by cells. It is a component of the plasma membrane of animal cells and the phospholipid bilayer. Being the outermost structure in animal cells, the plasma membrane is responsible for the transport of materials and cellular recognition; and it is involved in cell-to-cell communication.
Thus, steroids also play an important role in the structure and function of membranes. It has also been discovered that steroids can be active in the brain where they affect the nervous system, These neurosteroids alter electrical activity in the brain. They can either activate or tone down receptors that communicate messages from neurotransmitters. Since these neurosteroids can tone down receptors and decrease brain activity, steroids are often used in anesthetic medicines.
Privacy Policy. Skip to main content. Biological Macromolecules. Search for:. Lipid Molecules Fats and oils, which may be saturated or unsaturated, can be unhealthy but also serve important functions for plants and animals.
Learning Objectives Differentiate between saturated and unsaturated fatty acids. Key Takeaways Key Points Fats provide energy, insulation, and storage of fatty acids for many organisms. Fats may be saturated having single bonds or unsaturated having double bonds. Unsaturated fats may be cis hydrogens in same plane or trans hydrogens in two different planes.
Olive oil, a monounsaturated fat, has a single double bond whereas canola oil, a polyunsaturated fat, has more than one double bond. Omega-3 fatty acid and omega-6 fatty acid are essential for human biological processes, but they must be ingested in the diet because they cannot be synthesized.
Key Terms hydrogenation : The chemical reaction of hydrogen with another substance, especially with an unsaturated organic compound, and usually under the influence of temperature, pressure and catalysts. It contains the functional group carbon-oxygen double bond joined via carbon to another oxygen atom.
OH ; characteristic of carboxylic acids. Waxes Waxes are nonpolar lipids that plants and animals use for protection and have many functions in society. Learning Objectives Describe the roles played by waxes. Key Takeaways Key Points Natural waxes are typically esters of fatty acids and long chain alcohols. Animal wax esters are derived from a variety of carboxylic acids and fatty alcohols. Plant waxes are derived from mixtures of long-chain hydrocarbons containing functional groups. Because of their hydrophobic nature, waxes prevent water from sticking on plants and animals.
Elongation, fission F and breakage events B are indicated. In contrast to fission, a breakage event corresponds to a rupture at the level of the lipids where the pulling force is applied. C—F Dynamics of the acyl chains of asymmetric polyunsaturated phospholipids from all-atom simulations. The analysis was performed on flat membrane patches with the same composition as that used in the experiments.
C Velocity rate of the terminal CH 3 group of the acyl chain along either the membrane normal z velocity or in the membrane plane x-y velocity. E Number of protrusions of the CH 3 group above the glycerol group of phospholipids. Color code for coarse-grained simulations: grey: lipid polar head and glycerol; orange: acyl chain regions with double carbon bonds; yellow: acyl chain regions with single carbon bonds.
Color code for all-atom simulations: Grey: lipid polar head; cyan: glycerol; yellow: sn1 or sn2 acyl chains. During the time of the simulations ns , we observed fission events for some tubes formed from and membranes but not from or membranes Figure 6B , Figure 6—figure supplement 1A and Video 1. Although the number of simulations did not allow us to establish robust statistics, we noticed that the force threshold at which fission occurred was lower for membranes than for membranes Figure 6B and Figure 6—figure supplement 1B.
Moreover, fission occurred sooner for tubes as compared to tubes. Thus, the coarse-grained simulations agreed well with the experiments: the propensity of membranes to undergo deformation and fission correlates with the unsaturation level of the phospholipid sn2 acyl chain.
This video cannot be played in place because your browser does support HTML5 video. You may still download the video for offline viewing. For all-atom bilayers, we focused on parameters informative for the tendency of the phospholipid acyl chains to depart from the straight conformation. This tendency allows phospholipids to adopt different shapes and, consequently, to reduce the stress induced by membrane curvature Pinot et al. Figure 6C—E and Figure 6—figure supplement 2 show that whatever the parameter considered, the calculated value always increased with the polyunsaturation level of the sn2 chain, with clearly surpassing all other polyunsaturated FAs.
In contrast, the behavior of the sn1 chain was relatively constant and appeared poorly dependent on the nature of the neighboring sn2 chain. Altogether, these various analyses show that the main effect of having an sn2 polyunsaturated chain in phospholipids is to increase the probability of fast movements of along the z -axis.
To determine whether the membrane features endowed by the polyunsaturated acyl chain depend on its esterification at position sn2 as observed in natural lipids, we performed molecular dynamics simulations on phospholipid bilayers in which we swapped the sn1 and sn2 acyl chains Figure 6—figure supplement 3.
In all atom simulations, we observed that the rough features distinguishing the saturated and the polyunsaturated acyl chains remained after having permutated their position. These include z velocity, acyl chain torsions, and number of protrusions Figure 6—figure supplement 3A. However, measurements of the acyl chain density across the bilayer indicated that acyl chain swapping modified the mean position of the saturated and polyunsaturated acyl chains across the bilayer Figure 6—figure supplement 3B.
This effect probably resulted from the tilted orientation of glycerol, which makes the sn1 and sn2 positions not equivalent in term of z coordinates. In natural phospholipids, the density profile of the sn1 saturated FA showed a peak in the bilayer center whereas the sn2 polyunsaturated FA showed a characteristic dip. This shift indicates that the sn1 saturated FA tail invaded the central region of the bilayer left vacant by the sn2 polyunsaturated FA, which goes up Eldho et al.
With swapped phospholipids, this difference in density disappeared and the membrane appeared thinner than with natural phospholipids Figure 6—figure supplement 3B. Thus, the relative esterification position of the saturated and polyunsaturated FAs in natural lipids facilitates compensatory z movements where the polyunsaturated FA explores the interfacial region while the saturated FA explores the bilayer center.
In addition, acyl chain swapping did not significantly modify membrane fission Figure 6—figure supplement 3C and Video 2. Although a wealth of information is available on the interactions between endocytic proteins and specific lipids Puchkov and Haucke, , the role of the hydrophobic membrane matrix has been poorly investigated.
In vivo, manipulating the acyltransferases that are responsible for the large differences in the acyl chain profile of differentiated cells is challenging and is just starting to emerge Hashidate-Yoshida et al. In vitro, purified lipids are generally available from disparate sources e.
Synthetic lipids provide the best alternative but the most affordable ones generally display symmetric acyl chain combinations. This is exemplified by DOPS PS , which has allowed spectacular advances in our understanding of the structure of the dynamin spiral Chappie et al. Overall, the membrane templates on which dynamin and its partners have been studied are generally ill defined in terms of acyl chain profiles.
Our comprehensive analysis indicates that acyl chain asymmetry and acyl chain polyunsaturation have major effects on the mechanical activity of dynamin. A few studies have established that polyunsaturated phospholipids considerably modify the properties of membranes Armstrong et al.
For LUVs, a high dithionite permeability of membranes containing phospholipids has been reported Armstrong et al. For GUVs, micropipette manipulations indicate that the presence of at least one polyunsaturated acyl chain results in a drop of the membrane bending modulus whereas the presence of two polyunsaturated acyl chains causes a jump in water permeability Olbrich et al. These pioneer studies were performed on membranes made of a single lipid PC with a limited combination of acyl chains and in the absence of mechanically active proteins.
Depending on its acyl chain profile, a membrane can be either very resistant or very permissive to dynamin-mediated membrane vesiculation despite harboring the proper repertoire of polar head groups for protein recruitment.
However, these manipulations can also cause large changes in membrane permeability. Our analysis uncovers a narrow chemical window that allows phospholipid membranes to be both highly deformable and still impermeable to small solutes. Membranes with asymmetric saturated-polyunsaturated phospholipids such as or phospholipids are much less leaky than membranes with symmetrical or phospholipids but can still be readily vesiculated by dynamin provided that BAR-domain proteins are present.
Evidently, these features are advantageous for membranes such as synaptic membranes that undergo super-fast endocytosis Watanabe and Boucrot, Rotational freedom around these CH 2 groups is exceptionally high as compared to rotation around the CH 2 groups of monounsaturated or saturated acyl chains Feller et al. Such movements should allow phospholipids to readily adapt their conformation to membrane curvature Barelli and Antonny, ; Pinot et al.
Concurrently, the presence of a neighboring saturated acyl chain should secure lipid packing and prevents the passage of small molecules. Whether this model also accounts for the facilitation of the fission step per se remains, however, difficult to assess.
This step involves a change in membrane topology for which rare events such as protrusions of the terminal CH 3 groups could be decisive as they could nucleate bilayer merging or favor friction effects by proteins Simunovic et al. Other variations in the acyl chain content of mammalian phospholipids will deserve further investigations. First, we did not consider C acyl chains omega-6 or omega-3 , which are closer to C than C Eldho et al.
Although not abundant, C acyl chains are present in brain phospholipids Yabuuchi and O'Brien, Second, we did not study the influence of the linkage between the acyl chains and glycerol.
Plasmalogens, which form a large subclass of PE in the brain, harbor a sn1 saturated acyl chain that is bound to the glycerol through an ether-vinyl bond. Interestingly, ether-vinyl phospholipids considerably decrease the permeability of model membranes to ions because these lipids pack more tightly than their ester counterparts Zeng et al. The influence of plasmalogens on membrane flexibility and fission remains to be investigated.
Last, we only partially addressed the bias observed in natural phospholipids, where saturated and polyunsaturated acyl chains are preferentially esterified on different positions of the glycerol backbone sn1 and sn2 , respectively.
Testing this hypothesis by in vitro reconstitutions will require considerable efforts in lipid synthesis since swapped phospholipids are not commercially available. The abilities to vesiculate and to act as selective barriers are two fundamental properties of cellular membranes. Without membrane vesiculation, a cell cannot divide; without selective permeability, it cannot control the concentration of its nutrients.
Experiments aimed at mimicking the emergence of primitive membranes have illuminated how these properties need to be finally balanced. Single chain amphiphilic molecules e.
However, these bilayers are very leaky to even large solutes in the 10 3 Da range. Later, the shift from single chain to dual chain lipids has probably allowed primitive cells to reduce the general permeability of their membrane, thereby imposing an evolutionary pressure for the emergence of specialized transporters Budin and Szostak, The experiments presented here suggest that phospholipids with one saturated and one polyunsaturated acyl chain, which are absent in many eukaryotes e.
Proteins were purified as described Pinot et al. Dynamin was purified from rat brain using a recombinant amphiphysin-2 SH3 domain as an affinity ligand. Cells were lysed in 50 mM Tris pH 7. The supernatant was incubated with glutathione-Sepharose 4B beads followed by extensive washes in lysis buffer.
Endophilin was recovered in supernatant and further purified on a Superdex column in 20 mM Tris pH 7. Lipids were purchased from Avanti Polar Lipids as chloroform solutions see Key resources table.
These included the following species of phosphatidylcholine PC , phosphatidylethanolamine PE and phosphatidylserine PS : , , , , , , , , and Note that phospholipid species were custom-made lipids from Avanti.
Phosphatidylinositol 4,5 bisphosphate PIP 2 was from natural source brain. Submicrometer liposomes used for biochemical experiments and for electron microscopy were prepared by extrusion. A lipid film containing phospholipids and cholesterol at the desired molar ratio see Table S in supplementary file 1 was formed in a rotary evaporator and hydrated at a final lipid concentration of 1 mM in a freshly degassed HK buffer 50 mM Hepes pH 7. Calibrated liposomes were obtained by extrusion through or nm polycarbonate filters using a hand extruder Avanti Polar Lipids.
The size distribution of the liposomes was determined by dynamic light scattering at a final concentration of 0. All liposome suspensions were used within 1—2 days after extrusion. Special care was taken to minimize lipid oxidation by using fleshly degassed buffer supplemented with 1 mM DTT and by storing the liposome suspensions under argon.
Giant unilamellar vesicles were generated by electroformation as described Pinot et al. Lipid mixtures 0. After this step, sucrose mM osmotically equilibrated with buffers was added to the chamber. GUVs were electroformed Angelova et al. GTP hydrolysis in dynamin was measured using a colorimetric assay Leonard et al. Just before measurement, endophilin 0. At the indicated times 15, 45, 75, , , and s , aliquots 7. Fluorescence spectra of the PA probe with liposomes was performed as described Niko et al.
All spectra were corrected for the corresponding blank suspension of liposomes without the probe. Mixtures containing liposomes, dynamin, endophilin and nucleotides were prepared in HK buffer supplemented with 2. For the fission experiments in presence of GTP, vesicles were incubated for 30 min at room temperature.
Thereafter, an EM grid was put on the protein-liposome mixture for 5 min, rinsed with a droplet of mM Hepes pH 7. To determine the size distribution of the liposomes or of the protein-liposome profiles, to profiles for each condition and from three independent experiments were analyzed using the ellipse tool of the NIH Image J software. All experiments were performed with 0. After GUVs stabilization soluble Alexa was externally added to follow the entrance of the probe over time. Membrane fission induced by dynamin and endophilin in the presence of GTP was followed indirectly by monitoring the size of GUVs over time since the vesicles produced by the proteins are too small to be optically resolved.
We used a previously developed assay with some modifications Meinecke et al. The various systems were built with the Charmm-Gui tool Lee et al. Lipids not present in the Charmm-Gui database , , and and swapped lipids were built by adding unsaturations to related lipids i.
Note that one of this lipid is now present in the database and has the same topology as the one used here. The simulation parameters were those of Charmm-Gui under semi isotropic conditions within the NPT ensemble: x and y directions were coupled, whereas z direction was independent.
Periodic boundaries applied to all directions. We first equilibrated the membranes for ps using the standard Charmm-Gui six-step process during which constraints on lipids were gradually released. Next, an additional equilibration step was performed to equilibrate the TIP3P model of water. All simulations were equilibrated using the Berendsen thermostat and barostat at K and 1 bar, respectively, except for bilayers, which were equilibrated at K. Production runs were performed with the V-rescale thermostat at K except for bilayers K.
The Parrinello-Rahman thermostat was used to stabilize the pressure at 1 bar with a time constant of 5 ps and a compressibility of 4. The time step was set at 2 fs. Cutoff was fixed at 1. The smooth particle-mesh was used to evaluate the electrostatic interactions. Frames were saved every 10 ps. Trajectory analyses were performed from ns simulations from which we discarded the first ns in order to rule out processes that are not at equilibrium.
The remaining ns trajectory was divided in 3 blocks of ns to determine the standard deviation. Frames were analyzed every ps except for the velocity and permeability analysis for which we used 10 ps frames. The systems were built with the Charmm-Gui tool adapted to coarse-grained simulations Qi et al. In all simulations, we varied the acyl chains composition while keeping the PC polar head constant.
We used four lipids to approximate the asymmetric lipids , , , and Note that the coarse-grained simplification does not distinguish C from C, C from C, and C from C We built coarse-grained models of swapped phospholipids from natural phospholipids having acyl chains of the same length.
The systems contained 18 lipids and were solvated with a nm thick layer of water. The sytems were equilibrated with the standard Charmm-Gui six-step process. Production runs were performed with the V-rescale thermostat at K. The different membranes were simulated under a semi-isotropic condition and the periodic boundaries were applied in all directions. The time step was fixed at 20 fs and the cutoff for the Lennard-Jones and electrostatic interactions was set at 1.
This combination adds to the fluidity of the tails that are constantly in motion. The cell membrane consists of two adjacent layers of phospholipids, which form a bilayer. The fatty acid tails of phospholipids face inside, away from water, whereas the phosphate heads face the outward aqueous side. Since the heads face outward, one layer is exposed to the interior of the cell and one layer is exposed to the exterior. As the phosphate groups are polar and hydrophilic, they are attracted to water in the intracellular fluid.
As a result, there are two distinct aqueous compartments on each side of the membrane. This separation is essential for many biological functions, including cell communication and metabolism.
Biological membranes remain fluid because of the unsaturated hydrophobic tails, which prevent phospholipid molecules from packing together and forming a solid. If a drop of phospholipids are placed in water, the phospholipids spontaneously forms a structure known as a micelle, with their hydrophilic heads oriented toward the water.
Micelles are lipid molecules that arrange themselves in a spherical form in aqueous solution. The formation of a micelle is a response to the amphipathic nature of fatty acids, meaning that they contain both hydrophilic and hydrophobic regions.
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