Transport across the Plasma Membrane

Overview: Just passin' thru....

There are many ways in which a material can pass through the membrane. One such method is simple diffusion, which only occurs for small, nonpolar molecules (for example CO2 or O2). These molecules are small enough to squeeze between the phosphate heads of the phospholipids. Small polar molecules can also pass through, but usually the nonpolar fatty acids in the membrane repel them. The rate at which the small nonpolar molecules pass through is based upon the difference in concentration of that molecule on either side of the membrane. 

Facilitated Diffusion The second method by which molecules can move through the cell membrane is by passive transport. Passive transport allows highly polar molecules to move through the fatty acid layer which would normally not permit them to. One form of passive transport utilizes protein channels, whereby protein molecules in the membrane form a tunnel through which polar molecules may diffuse without ever coming in contact with the fatty acids. A second type of passive transport is known as facilitated diffusion. In this process, proteins called carrier proteins bond with the molecule on one side of the membrane, move through the membrane, and then release it on the other side. Like enzymes, carrier proteins usually bond with a specific molecule, but little else is known about them. 
Protein channel

In simple diffusion and passive transport, the cell did not expend any energy since the processes occurred naturally by diffusion and the free movement of proteins in the cell membrane. Another type of transport, called active transport, requires an input of energy by the cell








 Membrane proteins

Integral membrane proteins

Also referred to as transmembrane proteins. Commonly, integral membrane proteins have membrane spanning domains which are alpha helical. May be 1 , 2, 7 or more membrane spanning alpha helical domains. The alpha helix neutralizes the polar character of the peptide bonds. The hydrophobic side chains assoc. with these amino acids interact with the fatty acid chains of membrane lipids. Most transmembrane proteins are also glycosylated [have carbohydrate groups attached].

Peripheral membrane proteins
Not embedded in the bilayer but indirectly associated with the membrane through interactions with integral membrane proteins or by weak electrostatic interactions with the hydrophilic head groups of membrane lipids. Located extracellular or associated with the cytoplasmic surface of the bilayer.
  
Lipid-anchored proteins
Located outside the lipid bilayer, but covalently linked to a lipid molecule that is situated within the bilayer. An increasingly large number of proteins have been found to be linked by a short oligosaccharide to a molecule of glycophosphatidylinositol (GPI) that is embedded in the outer leaflet of the lipid bilayer. These proteins are released when membrane is treated with enzymes that (Phospholipases) that specifically recognized and cleaved inositol-containing phospholipids. Another group of proteins are actually present on the cytoplasmic side of the membrane and are anchored by long hydrocarbon chains embedded in the inner leaflet of the lipid bilayer.


THE GLYCOCALYX

The extracellular portion of the plasma membrane proteins are generally glycosylated. Likewise, the carbohydrate portions of glycolipids are exposed on the outer face of the plasma membrane. Consequently, the glycocalyx, is formed by the oligosaccharides of glycolipids and transmembrane glycoproteins.

Role:
Protection of cell surface
Markers for cell-cell interactions


TRANSPORT ACROSS CELL MEMBRANES
Membranes are selectively permeable --- small, uncharged molecules can diffuse freely through the phospholipid bilayer. O2, CO2. Also some small polar molecules H2O, ethanol and some small relatively hydrophobic molecules such as benzene.

Passive diffusion
Molecule simply dissolves in the phospholipid bilayer, diffuses across it, and then dissolves in the aqueous solution at the other side of the membrane. No membrane proteins involved in process. The net movement of molecules is simply according to the concentration gradient, with molecules moving from an area of higher concentration to an area of lower concentration.

Water is actually a rather special case - readily diffusable according to concentration gradient. Process is known as osmosis.

Larger polar molecules such as glucose cannot cross by passive diffusion. Charged ions also cannot [Na+, Ca++, K+, Cl-], even H+ cannot.
  
Facilitated Diffusion
Like passive diffusion, involves the movement of molecules in a net direction determined by concentration gradient---but with the assistance of specialized proteins.

Channel Proteins: Proteins which form open pores allowing for free passage of any molecule of appropriate size and charge by free diffusion. Form a passage through the lipid bilayer, allowing polar or charged molecules to cross without interacting with the hydrophobic fatty acid chains of the phospholipids.
ION CHANNELS-specific example of a channel protein. They are not permanently open [GATED]. There is a very wide variety of ion channels. All are integral membrane proteins that surround an aqueous pore. Bidirectional flow of ions based upon the electrochemical concentration gradient. Most channel proteins are said to be gated meaning that they can exist in open or closed conformation.

Carrier Proteins [Transporter Proteins]: Selectively bind and transport specific small molecules such as glucose. The molecules bind and the protein undergoes a conformational change that allows specific molecules to pass through. Involved in facilitated diffusion of sugars, amino acids, and nucleosides.

Active transport
Carrier proteins also provide a mechanism through which the energy changes associated with transporting molecules can be coupled to the use or production of other forms of metabolic energy.  Molecules can be transported against a concentration gradient if the transport is coupled to ATP hydrolysis, the absorption of light, the transport of electrons, or the flow of other substances down a gradient - as a source of energy.

Typically the K+ concentration inside a mammalian cell is about 100 mM, while that outside the cell is only 5mM. Diffusion of potassium out of the cell is favored. Sodium ions and Calcium ions have the opposite concentration gradient. Such gradients are maintained by active transport [ION PUMPS].

Depends on integral membrane proteins that are capable of selectively binding a particular solute and moving that substance across the membrane- driven by changes in the protein's conformation.

Vesicular Transport across the Plasma Membrane
   
The Endocytic Pathway

Uptake of macromolecules and particles is done by ENDOCYTOSIS.

Pinocytosis effectively internalizes portions of the cell membrane, any proteins or receptors on the membrane, and any ligands attached to those receptors. Fate of these receptors and their ligands varies after endocytosis. When soluble Ig binds to antigen, both receptor and ligand are directed to the lysosmes. The other possible route is that vesicles may be transported to another region of the membrane where the ligand is released.

One form of pinocytosis involves the use of coated pits [receptor-mediated endocytosis]. Ligand binds to receptor. Complex travels laterally through the membrane to a coated pit region. Complexes are retained and concentrated in these pits. Clathrin is a protein whose subunits form the surface of the pit. Pit then invaginates and eventually forms a vesicle known as a clathrin coated vesicle. The clathrin coated vesicle first fused with vesicles known as early endosomes. Fusion with the early endosome brings the pH of the clathrin coated vesicle down to between pH 6 and 6.2. This shift to an acidic pH allows the clathrin and the receptor to be transported back to the surface. Late endosomes then fuse with the vesicle, further lowering the pH to between 5.5-6.0. Finally, lysosomes fuse bringing the pH down to about 5.0. Lysosomes also release a battery of hydrolytic enzymes that digest the material remaining in the vesicle.

The other major form of endocytosis is termed: Phagocytosis. Phagocytosis can only be carried out by phagocytic cells such as macrophages and neutrophils. Phagocytosis involves the internalization of particles such as bacteria, protozoa, etc. In the process of phagocytosis, the particle first binds to the phagocytic cell, then the cell sends out extensions of the cyotplasm known as pseudopodia which surround the particle. The formation of psuedopodia is dependent upon the polymerization of the cytoskeletal protein, actin. The internalized particle is now enclosed in a membrane-bound structure known as a phagosome. Lysosmes subsequently fuse with the phagosome forming a phagoslysosome. The hydrolytic enzymes released by the lysosome function in the digestion of the internalized particle.
  
Exocytosis
Material enclosed in a cell vacuole is passed to the extracellular fluid by fusion of the vacuole with the plasma membrane. Secretory process and a mechanisim of replenishing lipids and proteins of plasma membrane.