<P> Polar molecules and large ions dissolved in water cannot diffuse freely across the plasma membrane due to the hydrophobic nature of the fatty acid tails of the phospholipids that make up the lipid bilayer . Only small, non-polar molecules, such as oxygen and carbon dioxide, can diffuse easily across the membrane . Hence, no nonpolar molecules are transported by proteins in the form of transmembrane channels . These channels are gated, meaning that they open and close, and thus deregulate the flow of ions or small polar molecules across membranes, sometimes against the osmotic gradient . Larger molecules are transported by transmembrane carrier proteins, such as permeases, that change their conformation as the molecules are carried across (e.g. glucose or amino acids). Non-polar molecules, such as retinol or lipids, are poorly soluble in water . They are transported through aqueous compartments of cells or through extracellular space by water - soluble carriers (e.g. retinol binding protein). The metabolites are not altered because no energy is required for facilitated diffusion . Only permease changes its shape in order to transport metabolites . The form of transport through a cell membrane in which a metabolite is modified is called group translocation transportation . </P> <P> Glucose, sodium ions, and chloride ions are just a few examples of molecules and ions that must efficiently cross the plasma membrane but to which the lipid bilayer of the membrane is virtually impermeable . Their transport must therefore be "facilitated" by proteins that span the membrane and provide an alternative route or bypass mechanism . </P> <P> Various attempts have been made by engineers to mimic the process of facilitated transport in synthetic (i.e., non-biological) membranes for use in industrial - scale gas and liquid separations, but these have met with limited success to date, most often for reasons related to poor carrier stability and / or dissociation of the carrier from the passive transport . </P> <P> In living organisms, the main physical and biochemical processes that are required for survival are regulated by diffusion . Facilitated diffusion is one form of diffusion and it is important in several metabolic processes of living cells . One vital role of facilitated diffusion is that it is the main mechanism behind the binding of Transcription Factors (TFs) to designated target sites on the DNA molecule . The in vitro model, which is a very well known method of facilitated diffusion, that takes place outside of a living cell, explains the 3 - dimensional pattern of diffusion in the cytosol and the 1 - dimensional diffusion along the DNA contour . After carrying out extensive research on processes occurring out of the cell, this mechanism was generally accepted but there was a need to verify that this mechanism could take place in vivo or inside of living cells . Bauer & Metzler (2013) therefore carried out an experiment using a bacterial genome in which they investigated the average time for TF--DNA binding to occur . After analyzing the process for the time it takes for TF's to diffuse across the contour and cytoplasm of the bacteria's DNA, it was concluded that in vitro and in vivo are similar in that the association and dissociation rates of TF's to and from the DNA are similar in both . Also, on the DNA contour, the motion is slower and target sites are easy to localize while in the cytoplasm, the motion is faster but the TF's are not sensitive to their targets and so binding is restricted . </P>

All of the following affect the rate of simple diffusion except