The lipid bilayer is a thin polar membrane made of two layers of lipid molecules. These membranes are flat sheets that form a continuous barrier around all cells. The cell membranes of almost all living organisms and many viruses are made of a lipid bilayer, as are the membranes surrounding the cell nucleus and other sub-cellular structures. The lipid bilayer is the barrier that keeps ions, proteins and other molecules where they are needed and prevents them from diffusing into areas where they should not be. Lipid bilayers are ideally suited to this role because, even though they are only a few nanometers in width, they are impermeable to most water-soluble (hydrophilic) molecules. Bilayers are particularly impermeable to ions, which allows cells to regulate salt concentrations and pH by transporting ions across their membranes using proteins called ion pumps. Natural bilayers are usually composed of phospholipids, which have a hydrophilic head and two hydrophobic tails each. When phospholipids are exposed to water, they arrange themselves into a two-layered sheet (a bilayer) with all of their tails pointing toward the center of the sheet. The center of this bilayer contains almost no water and excludes molecules like sugars or salts that dissolve in water but not in oil. This assembly process is similar to the coalescing of oil droplets in water and is driven by the same force, called the hydrophobic effect. Because lipid bilayers are quite fragile and are so thin that they are invisible in a traditional microscope, bilayers are very challenging to study. Experiments on bilayers often require advanced techniques like electron microscopy and atomic force microscopy. Phospholipids with certain head groups can alter the surface chemistry of a bilayer and can, for example, serve as signals as well as “anchors” for other molecules in the membranes of cells. Just like the heads, the tails of lipids can also affect membrane properties, for instance by determining the phase of the bilayer. The bilayer can adopt a solid gel phase state at lower temperatures but undergo phase transition to a fluid state at higher temperatures, and the chemical properties of the lipids’ tails influence at which temperature this happens. The packing of lipids within the bilayer also affects its mechanical properties, including its resistance to stretching and bending. Many of these properties have been studied with the use of artificial “model” bilayers produced in a lab. Vesicles made by model bilayers have also been used clinically to deliver drugs. Biological membranes typically include several types of lipids other than phospholipids. A particularly important example in animal cells is cholesterol, which helps strengthen the bilayer and decrease its permeability. Cholesterol also helps regulate the activity of certain integral membrane proteins. Integral membrane proteins function when incorporated into a lipid bilayer, and they are held tightly to lipid bilayer with the help of an annular lipid shell. Because bilayers define the boundaries of the cell and its compartments, these membrane proteins are involved in many intra- and inter-cellular signaling processes. Certain kinds of membrane proteins are involved in the process of fusing two bilayers together. This fusion allows the joining of two distinct structures as in the fertilization of an egg by sperm or the entry of a virus into a cell.