5.3Functions of Biological Membranes
A cell is a compartment separated from its outer environment by a plasma membrane. The interior of a eukaryotic cell is also compartmentalized into many organelles, and different reactions occur in each compartment.
Since lipids are the basic constituents of biological membranes (as shown in Fig. 5-4A), small, electrically non-charged solutes such as ethanol, oxygen and carbon dioxide can pass through a lipid bilayer by simple diffusion following the concentration gradient. Water-soluble ions (Na+, K+ and Cl-), sugars (e.g., glucose) and amino acids, however, cannot pass through the membrane. Proteins - high molecules - are also unable to penetrate. By rigorously regulating the transport of these materials, the plasma membrane keeps the intracellular environment relatively stable even when the outside environment changes.
As shown in Figure. 5-4B, the plasma membrane has membrane proteins such as transporters that transport specific molecules, and channels that let specific molecules pass. Most solutes can pass through the membrane only when transported by membrane proteins. In this case, passive transport (i.e., transport following the concentration gradient) occurs without relying on energy, whereas active transport (i.e., transport against the concentration gradient) requires energy. Active transport is performed by transporters.
The mechanism of active transport, which uses energy, is shown in Figure. 5-5. Animal cells have a higher K+ concentration and a lower a+ concentration than blood. To maintain these conditions, an Na+/K+ pump - a type of transporter - transports Na+ ions to the outside and K+ ions to the inside of the cell against the concentration gradient using the energy generated when ATP is hydrolyzed into ADP. A pump protein containing Na+ attached to (1) is phosphorylated using the energy generated through the hydrolysis of ATP and changes its structure (2), releases Na+ to the outside of the cell (3), and catches Ka+ instead (4). The pump protein is then dephosphorylated (5) and changes its structure, releasing K+ into the cell (6). These reactions occur continually, using 30% of the energy generated within the cell in some animal cells.
In this case, the energy of ATP is used twice for the structural changes of pump proteins caused by phosphorylation and dephosphorylation, which allows the transport of Na+ and K+.
Fig. 5-4. The plasma membrane - a lipid bilayer that serves as a barrier against solutes and regulates the passing of material by transporters and channels
The plasma membrane lets small, electrically non-charged solutes with a low molecular weight pass, but forms a barrier against ions and large solutes that have a high molecular weight (A) and regulates transport by transporters and channels. Passive transport occurs when the concentration gradient is followed, but active transport, which requires energy, takes place using ATP-derived or other energies when transport occurs against the concentration gradient (B).
Cholesterol in the Plasma membrane
The nature of the plasma membrane varies greatly depending on its lipid composition. Main lipids of the plasma membrane include phospholipids, sterols and glycolipids. A typical phospholipid is phosphatidylcholine (Column Fig. 5-1A). The head, consisting of choline and phosphate, is connected by glycerol with hydrocarbon tails that look like two legs. The fluidity of the membrane changes significantly depending on how many double bonds these hydrocarbon tails have. A double bond formed between carbon and carbon bends the hydrocarbon chain from that point.
The most abundant constituent in the membrane of animal cells is cholesterol (Column Fig. 5-1B). This short, hard molecule is mainly located on the inside of the plasma membrane, and fills the gaps created by the double-bond bending of phospholipids.
The plasma membrane has sites called rafts where cholesterol and glycolipids are concentrated. In rafts, membrane lipids become like liquid crystal and hence have low fluidity. It is known that membrane proteins involved in signaling tend to be concentrated in rafts.
Lipid-modified proteins move from the cytoplasm to the inside of rafts, whose outside has many glycolipids and attracts glycolipid-modified proteins.
Membrane regions rich in cholesterol are associated with neurological and immunological functions, Alzheimer's disease and viral infection, and are therefore quite well known. Lipid-rich regions of the plasma membrane, such as rafts, are known as the micro-domains of the membrane.
In a resting (non-excited) cell, electrical potential difference exists whereby the interior of the cell separated by the plasma membrane has negative potential (i.e., resting membrane potential). This is due to the difference in ion concentration between the inside and the outside of the cell (Table 5-2) and the selective permeability of the plasma membrane for ions (Fig. 5-6). With the plasma membrane in a resting state, certain K+ channels are kept open; the membrane can therefore be thought of as a semipermeable membrane that allows K+ ions to pass. When a difference in the concentration of K+ exists between either side of such a semipermeable membrane, the resting membrane potential is calculated as approximately -90 mV by the Nernst equation (see the Column in 5.4). This potential is similar to the value for an actual cell, but differs slightly because small amounts of Na+ and Cl- also pass through actual plasma membranes.
Additionally, in excitable cells such as neurons, further special changes in membrane potential occur in response to changes in the resting membrane potential caused by stimuli (see the Colum in 5.4).
Fig. 5-6. Generation of membrane potential by a K+ channel
When a K+ channel opens, releasing only K+ ions inside the cell to the outside, membrane potential is generated unless ions with a negative charge are also released to balance out the positive ions. The movement of K+ stops at the point where the driving force of K+ following the gradient of membrane potential and the driving force of K+ following the concentration gradient balance each other out. Refer to the Column in 5.4 for the calculation of this point.
Proteins that Bind to the Membrane without a Transmembrane Structure
Among the proteins that are attracted to the membrane, many do not have a membrane-spanning structure; rather, they covalently bond to lipids. The hydrophobic part of the hydrocarbon of lipids bonded to these proteins is incorporated into the lipid bilayer of biological membranes and accumulates on them. As shown in Column Figure. 5-2, whether a protein binds to the inside or the outside of the membrane depends on the lipid type attached to it. As an example, proteins modified by palmitic acid or myristic acid bond to the inside of the plasma membrane, while those modified by glycolipids bond to the outside. Other types of protein attracted to the membrane include those that recognize the special structure of membrane lipids. As an example, phosphatidylinositol - a membrane lipid - is phosphorylated at the proteins 3’, 4’ and 5’ in Column Figure. 5-2C. In such cases, specific proteins that bind to phosphorylated lipids exist, and different proteins are attracted to the membrane each time the membrane lipids are phosphorylated or dephosphorylated.
Column Fig. 5-2. On the plasma membrane, proteins modified by lipids and proteins that attach themselves to particular lipids also accumulate
A) Accumulation of lipid-modified proteins on the biological membrane,
B) Structure of phosphatidylinositol, C) Proteins that recognize phosphorylated phosphatidylinositol
Signaling by Receptors
Information on the outside of the cell is transmitted to the inside via receptors in the plasma membrane. This mechanism is discussed in detail in Chapter 9-1.
Connection to the Cytoskeleton and the Extracellular Matrix via the Plasma membrane