Revision:Pre-clinical: Cell Structure 1: The Cell Surface

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Structural Overview

Diagrammatic representation of the phospholipid bilayer component of the cell surface membrane (click to enlarge)

Ok chaps, it’s GCSE biology revision time. Cells are contained within a membrane; specifically a lipid bi-layer - mostly phospholipids. These exist as a bi-layer due to the nature of these lipids: these posses hydrophilic ‘heads’ and hydrophobic ‘tails’, which thus align as per the diagram to appropriate orientation considering the hydrated nature of the cytosol and the extracellular contents. Proteins such as receptors, ion channels and transporters are inserted into and through this bi-layer, as well as cholesterol - a (non-phospho)lipid which increases the rigidity of the membrane.

Cholesterol is intercalated between between the phospholipids of the membrane, and due to its small and rigid nature (due to the planar steroid ring structure that makes up much of the molecule) reduces the fluidity and permeability of the membrane.

The insertion of integral membrane proteins takes advantage of the structure of the surface membrane: the trans-membrane domains of these proteins are predominantly hydrophobic due to hydrogen bonding within α-helix structures, presenting hydrophobic amino acids to the outside of the protein, where they exist stably in contact with the lipids that surround them. Proteins that exist in the surface membrane include transporters (exempli gratia pumps and channels); integrin anchors, chemical receptors and signal transduction molecules.

The fluid nature of the surface membrane is important: it allows signalling lipids and proteins to easily and quickly diffuse across it; permits fusion with other membrane, thus enabling endocytosis, exocytosis et cetera and ensures that the surface membrane is equally shared between daughter cells during cytokinesis.

Transport across membranes

Diagrammatic representation of relative permeability via simple diffusion of a phospholipid bilayer if it had no transmembrane proteins (click to enlarge)

Transport across cell membranes occurs in two ways - either passively or actively. As their names suggest, the former requires no energy input, whilst the latter does.

Passive transport occurs by either simple or facilitated diffusion: simple diffusion occurs across the membrane itself, whilst facilitated diffusion occurs through membrane protein channels - neither requires energy input as both are driven by the electrochemical gradient.

Not all molecules can diffuse through the lipid bi-layer itself (see diagram), hence requiring the presence of membrane proteins that will allow them entry. There are two classes of these proteins that are involved in facilitated diffusion: channels and uniporter carrier proteins.

Active transport moves solutes regardless of the electrochemical gradient; and as such often against it and thus requires energy input to drive this movement; this will be covered further on.

Passive transport - Facilitated Diffusion

Channels

Channels are proteins that form hydrophilic pores in the surface membrane of a cell: hydrophilic surfaces on the interior of the protein permit this aperture to allow non-directional flow of solutes across the membrane. The most common channels are non-directional ion channels.

Channels do show some selectivity, however this is almost always based upon the size and charge of the species attempting to flow through them. The potential rate of diffusion through these channels is also very large - up to 107 ions per second.

Channels may be gated to allow them to be closed or opened - though the processes involved in doing so may require energy, diffusion when open is still a passive process. This allows greater control over the flow of ions in and out of cells, an example being the voltage-gated Na+ and K+ channels that are so important to the propagation of action potentials in neurones.

Uniporter Carrier Proteins

Uniporters are highly selective proteins to which substrates bind, thereby changing the uniporter’s conformation resulting in the substrate being released on the other side of the membrane. Almost all small organic molecules - exempli gratia glucose - require these carrier proteins to diffuse across cell membranes. It is important to note that uniporter carrier proteins are NOT a form of active transport and should not be confused with coupled transporters (covered further on) - they are powered by the diffusion gradient of the substrate itself and thus only move a substrate along its concentration gradient.

Active Transport

Active transport moves solutes regardless of the electrochemical gradient; and as such often against it and thus requires energy input to drive this movement. Active transport is very important, as it is key to maintaining electrochemical gradients to perpetuate passive transport; acquiring and removing molecules too large to diffuse through the membrane or channels and maintaining osmotic balance.

For example, the Na⁺K⁺ATPase pump binds 3Na⁺ (on the cytosolic side) and hydrolyses ATP to ADP + P_i. The bonding of the inorganic phosphate to the antiporter changes its conformation, releasing the Na+ extracellularly, and allowing 2K⁺ to bind to the extracellular surface of the protein. This triggers the removal of the phosphate, returning the pump to its original conformation and releasing the 2K⁺ into the cytosol et vice versa. This cycle takes about ten milliseconds.

This antiporter is very important, as it removes Na⁺ from the cell - it enters constantly from ion channels and other carrier proteins. Indeed, the operation of this protein accounts for 30% of a cell’s total energy expenditure.

There are three main types of active transporters:

1. Coupled transporters - symporters and antiporters which do not require ATP - transport a substrate against its concentration gradient by coupling its transport to another substrate which the transporter moves along its electrochemical gradient, thus providing the driving force (active transport because it requires the energy from one gradient to move the other ion). The gradient of the substrate moving along its gradient is often maintained by primary active transport elsewhere. [Secondary Active Transport]
   
   
2. ATPases - such as Na⁺K⁺ATPase - these couple the transport of a solute against its concentration gradient to the hydrolysis of ATP. [Primary Active Transport]
   
   
3. Light driven pumps - as their name suggests, couple the transport of a solute against its concentration gradient to energy provided by light (as one might suspect, not prevalent in humans; moreso in photosynthetic organisms).

In case any one finds it hard to memorise or understand, I'll provide a very brief classics lesson here which will hopefully make antiporters and symporters clear: a symporter moves both of the coupled solutes in the same direction, whilst an antiporter moves them in opposite directions - their names make sense, therefore, as ‘Sym-’/’Syn-’ is ancient Greek for ‘together’, ‘Anti-’ for against.

An example of a symporter is the Na⁺/Glc symporter in the gut. [Glc] is low in the gut lumen and high intracellularly (due to both active transport and facilitated diffusion via the GLUT2 carrier protein), whilst [Na⁺] is high in the gut lumen and low intracellularly. The potential energy of the Na⁺ electrochemical gradient is thus exploited to actively transport more glucose into the gut epithelial cell; binding of 2Glc and 2Na⁺ extracellularly triggers the release of both intracellularly. Though this is not technically a one-way gated protein, in practice it may as well be; net diffusion is always massively inwards since the action of the symporter requires the binding of Na⁺, which is far more concentrated extracellularly.

The Na⁺Ca⁺ antiporter (or ‘exchanger’) is important in cardiac muscle, where it removes calcium from the cells, relaxing them (or reducing the strength of contraction). It is also significant in neurones, where at the synaptic bouton Ca⁺ has to be quickly removed after the influx caused by neurotransmitter activation of Ca⁺ channels; the operation of this antiporter that exchanges extracellular 3Na⁺ also serves to propagate the action potential.

Another example of primary active transport (having looked at Na⁺K⁺ATPase earlier) is the proton pump; acting simply to transport H⁺ from one side of the membrane to the other against its gradient, energy provided courtesy of the lysis of ATP to ADP + P_i. Prokaryotes use this pump and H⁺ instead of Na⁺ for coupled transport, but of more relevance to us is the pump’s function in the human body; where lysosomes, phagosomes and mitochondria use them to regulate and localise acidity and, in the case of mitochondria, build a chemical gradient that is used to synthesise ATP (in mitochondria, the energy for this is provided in the electron transport chain from the oxidation of NADH and FADH₂; as part of the energy released in the production of ATP in respiration).