The three ways lipid structure relates to membrane function
- Membrane curvature
- Bilayer asymmetry
- Membrane fluidity
1. Membrane curvature
In curved portions, if the lipids in the outer leaflet of the membrane are cylindrical, then some of the lipids in the inner leaflet need to be conical to maintain structural integrity.
For example, phosphatidylcholine (PC), which is cylindrical, tends be more abundant in the outer leaflet, while phosphatidylethanolamine (PS), which is conical, is more abundant in the inner leaflet.
2. Bilayer Asymmetry (drives function)
There are many types of lipids found in membranes. In red blood cells (RBC), for example, some of the inner leaflet lipids have a net negative charge. The specific concave shape of a RBC is driven by the distribution of these various lipid types. This shape is also critical to its functionality. Now as RBCs age, their asymmetric distribution changes. Previously interior lipids move to the surface, which then acts as a signal to microphage for those cells to be cleared out.
While membrane lipids can move around laterally, to “flip” from one leaflet to the other is thermodynamically unfavorable since the hydrophilic head would have to cross the hydrophobic core of the membrane. But this does happen thanks to a group of three helper proteins:
- Flippase moves a lipid from the outer leaflet to the inner against its concentration gradient.
- Floppase does the same thing in the opposite direction, inner to outer.
- Scramblase moves the lipid in both directions, always going with the concentration gradient.
Thus, flippase and floppase maintain membrane asymmetry, while scramblase erases it.
The relation between asymmetric composition of membranes and the site of lipid synthesis
Lipids are typically synthesized in the Endoplasmic Reticulum (ER) and follow the same pathway as proteins: ER to the Golgi to the membrane, transported from one to the other by transport vesicles, the difference being that lipids get embedded in the membranes of each along the way.
One lipid, sphingomyelin, is synthesized in the luminal face of the Golgi, instead of the ER, and is thus more abundant there. In the Golgi, it gets embedded in its inner leaflet. Later, it gets embedded into the inner leaflet of the vesicles that transport it to the cell membrane. However, when the vesicle fuses with the cell membrane, the inner leaflet of the vesicle gets placed onto the outer leaflet of the membrane. And so sphingomyelin appears on the outer leaflet of cell membranes, a direct result of its mode of synthesis.
3. Membrane Fluidity
The rules for the “packing” of phospholipids are similar to those of melting points: saturated, long fatty acids will pack in a dense, regular structures with low fluidity called the paracystalline state. Short, unsaturated fatty acids will pack irregularly and be more fluid.
However, at physiologic conditions a membrane exists in an intermediate state of fluidity between paracystalline and irregular.
The Role of Cholesterol
Cholesterol is a structural lipid different from the other structural lipids. It’s flat. It has rings. During the commute from the Golgi to the cell membrane, a fraction of phosphatidylcholine is replaced by sphingomyelin, which is why cholesterol is so abundant in the cell membrane.
In a cell membrane, cholesterol alters the mobility of fatty acids with short, unsaturated tails by decreasing their fluidity. In contrast, it also disrupts the long, saturated phospholipids, disturbing their tight packing, preventing paracystalline structures from forming, and thereby increasing their fluidity. So it serves as a balancing mechanism to keep the membrane in its “sweet spot.”