Diffusion is essentially the movement of molecules from a region of higher concentration to a region of lower concentration as a result of thermal motion. Diffusion is an important process in human physiology. Specifically, diffusion is the mechanism of movement of oxygen, nutrients and other molecules across the capillary walls and the movement of other molecules across membranes. The amount of material crossing a surface per unit of time is called flux and depends upon the difference in concentrations between two compartments where movement is potentially going to occur. When diffusion between two compartments is equal, meaning no net movement, the system has reached diffusion equilibrium. Net flux is zero and there are no further changes in concentration. Difference in concentration, temperature, and surface area of diffusion are all positively correlated with direction and magnitude of net flux. While the mass of molecules in solution are negatively correlated with direction and magnitude of net flux. The time that it takes for diffusion to occur increases in proportion to the square of the distance over which molecules diffuse. Diffusion, therefore, is only useful for moving molecules over small distances.
Diffusion through Membranes
The magnitude of net flux can be measured as:
F= kpA(C0 – Ci) where,
kp = permeability constant for a particular molecule at a particular temperature
A = surface area of membrane
C0 = extracellular concentration of the substance
Ci = intracellular concentration of the substance
Remember that membranes slow down diffusion and molecules will move slowly than through a water layer of equal thickness. i.e. for structural reasons a water layer is easier than a membrane to diffuse through.
Role of Electric Forces on Ion Movement
Membrane potential is the separation of electric charges across a membrane. The separation of charges influences the movement of ions across the membrane. This can act independently of or in conjunction with, or in opposition to, the force generated by concentration differences. Electrochemical gradient refers to these two forces collectively: the force due to charges and the force due to concentration differences.
Diffusion through the Lipid Bi-layer
Non-polar molecules can dissolve in the non-polar fatty acid chains of the membrane phospholipids and therefore non-polar molecules have larger permeability constants than polar molecules.
Diffusion of Ions through Protein Channels
Protein channels formed by integral proteins allow ions to diffuse across the membrane. Different cells have different permeabilities to these ions. The diameter of the channel and the polar groups on the protein subunits forming channel walls determine the permeability of the channels by various ions and molecules.
Regulation of Diffusion through Ion Channels
Channel gating is the opening and closing of ion channels which changes the permeability of a membrane. It is controlled by three modulators:
- Modulation of allosteric or covalent channel-proteins in ligand-sensitive channels
- Modulation of channel proteins due to changes due to changes in membrane potential in voltage-gated channels.
- Modulation of channel proteins due to stretching in mechanosensitive channels.
Several factors and influence a single channel and any one ion can pass through several different channels.
Mediated Transport Systems
There are integral membrane proteins called transporters that mediate movement of molecules that are too polar or too large to move across a membrane by diffusion.
In order to accomplish this, a solute (molecule to be transported) binds to a specific site on a transporter on one surface of the membrane. The transporter then changes shape in order to expose the bound solute to the opposite side of the membrane. The solute then dissociates from the transporter and finds itself on the other side of where it started. Depending on the membrane, and the needs of the cellular environment, there may be many types of transporters present with specific binding sites for particular types of substances. Solute flux magnitude through a mediated transport system is positively correlated with the number of transporters, the rate of conformational change in the transporter protein, and the overall saturation of transporter binding sites which is dependent on the solute concentration and affinity of the transporter. These are important factors to consider in getting large materials through a membrane.
Facilitated diffusion moves solutes from a region of higher concentration to a region of lower concentration until the concentrations become equalized on both sides of the membrane.
This form of molecule movement requires energy in order to move solute against its electrochemical gradient. Energy is required to either:
- Alter the affinity of the binding site on different sides of the membrane
- Alter the rates at which the binding site on the transporters is shifted from one side of the membrane to the other.
Furthermore, there are two ways in which a flow of energy can be coupled to transporters.
- Primary active transport requires energy is provided by ATPase.
Sodium, potassium—ATPase (Na, K—ATPase) is present in plasma membranes which works by moving 3 Na+ ions out of a cell and 2 K+ ions in, resulting in a net transfer of positive charge outside the membrane.
Calcium—ATPase in plasma membranes moves Ca2+ ions from the cytosol to the extracellular fluid, while Ca—ATPase in membranes of organelles moves Ca2+ from cytosol into the organelle lumen (space).
Hydrogen—ATPase in plasma membranes moves hydrogen ions (H+ or protons) out of cells.
- Secondary active transport provides energy from the flow of ions from an area of higher concentration to one of lower concentration. Allosteric modulation modifies the affinity of the binding site. There are technically two types of secondary active transport.
- Cotransport occurs if a molecule moves in the same direction as the ion providing the energy. An example is the movement of amino acids using sodium ions.
- Countertransport occurs when the molecule moves in the opposite direction as the ion providing the energy. An example is the movement of calcium ions using sodium ions.
In sum, with ions the movement is from high to low concentration, and molecules from low to high.
Osmosis is the net diffusion of water across a membrane. Aquaporins are proteins that form channels in the lipid bi-layer for the polar water molecules to diffuse through. There will be a net diffusion of both compartments leading to diffusion equilibrium with no change in volume in either compartment if the compartments are separated by a membrane that is permeable to both a solute and water. However, if the membrane is only permeable to water (i.e. not to the solute) then diffusion equilibrium will be reached with a net increase in volume of the compartment that had a higher osmolarity to begin with. Osmolarity is the total solute concentration of a solution and is measured in units called osmols. Therefore, water concentration in a solution is negatively correlated with the number of solute particles. Osmotic pressure is the pressure that must be applied to prevent the net flow of water into a solution separated by a membrane. The osmotic pressure increases with increases in osmolarity. Water will then move from regions of lower osmotic pressure to regions of higher osmotic pressure.
When a system reaches equilibrium, the osmolarities of intra- and extracellular fluids are the same. An isotonic solution is a solution which cells will neither swell nor shrink, this is assuming that the cells are placed into a solution of non-penetrating solutes with the same osmolarity as the extracellular fluid. The key thing is that there is no net movement in an isotonic solution. In an hypotonic solution, the solution contains less non-penetrating solutes, and the cells therefore absorb water and the cells swell. Finally, a hypertonic solution is one in which the solution contains more non-penetrating solutes and water moves out of the cells and they shrink. It is important to understand that penetrating solutes do not contribute to the tonicity of the solution.
Endocytosis is a transportation process that requires energy. The main mechanism is that regions of the plasma membrane fold into the cell which forms small pockets on the inside of the cell. These pockets pinch off into membrane-bound vesicles inside the cell.
Fluid endocytosis refers to when the vesicles formed enclose a small volume of extracellular fluid. However, if certain molecules in the extracellular fluid happen to bind to specific proteins on the plasma membrane and are then carried into the cells with extracellular fluid, the process is then called adsorptive endocytosis. Collectively, these two processes are also called pinocytosis and are demonstrated by most cells.
Some cells will engulf large foreign particles via a process called phagocytosis. This only happens in specialized cells that are relatively few in number and occurrence. The type of particles engulfed include bacteria and cell debris.
Endosomes are usually fused with endocytic vesicles at some point in the process, and the contents of the packets are then passed into organelles such as Lysosomes.
Both pinocytosis and phagocytosis are examples of endocytic processes. The big thing to remember is that the movement of particles is from the outside of the plasma membrane to the inside.
In order to move things from the inside of the cell to the outside, membrane-bound vesicles in the cytoplasm will fuse with the plasma membrane and release their contents outside the cell. The bound vesicle material then assimilates into the plasma membrane. In this fashion, portions of the plasma membrane lost during endocytosis can be replaced. Additionally, the process provides a route by which membrane impermeable molecules, such as protein hormones, that are synthesized by cells can be released into the extracellular fluid. Finally, the process of exocytosis is triggered by stimuli that leads to an increase in cystolic calcium concentration which in turn activates proteins required for the vesicle membrane to fuse with the plasma membrane and thus repairing any ‘holes’ from prior processes.
The luminal (or apical or mucosal) membrane is the plasma membrane surface of an epithelial cell that faces a hollow or fluid filled chamber. The basolateral (or serosal) membrane is the surface of plasma membrane on the opposite side usually adjacent to a network of blood vessels.
Substances can cross a layer of epithelial cells via two pathways.
- The paracellular pathway refers to diffusion between adjacent cells in the epithelium. This pathway is limited to small ions and water because of the presence of tight junctions.
- The transcellular pathway refers to the movement into an epithelial cell from one side, then diffusion through the cytosol and exit through the opposing membrane.
The transport and permeability characteristics of the luminal and basolateral membranes are not the same due to the presence of different ion channels and transporters. Substances, therefore, are able to move from a region of lower concentration on one side to a higher concentration on the other.
Gland cells secrete organic molecules synthesized by their own cellular processes and they also secrete salts and water, moving them from one extracellular compartment to another.
The rate of secretion is controlled by chemical or neural signals and work by:
- Altering the rate of synthesis
- Altering the rate of exocytosis via calcium channels
- Altering the pumping rate of transporters and opening rate of ion channels
Two types of glands:
- Endocrine glands will release their secretions directly into the interstitial fluid surrounding the gland cells. Endocrine glands secrete hormones.
- Exocrine glands utilize ductworks in order to connect to epithelial surfaces. The secretions flow through the ductworks or onto the surface of the epithelium. Sweat and salivary glands are examples of exocrine function.