<P> Thus, by the early twentieth century the chemical, but not the structural nature of the cell membrane was known . Two experiments in 1924 laid the groundwork to fill in this gap . By measuring the capacitance of erythrocyte solutions Fricke determined that the cell membrane was 3.3 nm thick . Although the results of this experiment were accurate, Fricke misinterpreted the data to mean that the cell membrane is a single molecular layer . Because the polar lipid headgroups are fully hydrated, they do not show up in a capacitance measurement meaning that this experiment actually measured the thickness of the hydrocarbon core, not the whole bilayer . Gorter and Grendel approached the problem from a different perspective, performing a solvent extraction of erythrocyte lipids and spreading the resulting material as a monolayer on a Langmuir - Blodgett trough . When they compared the area of the monolayer to the surface area of the cells, they found a ratio of two to one . Later analyses of this experiment showed several problems including an incorrect monolayer pressure, incomplete lipid extraction and a miscalculation of cell surface area . In spite of these issues the fundamental conclusion - that the cell membrane is a lipid bilayer - was correct . </P> <P> A decade later, Davson and Danielli proposed a modification to this concept . In their model, the lipid bilayer was coated on either side with a layer of globular proteins . According to their view, this protein coat had no particular structure and was simply formed by adsorption from solution . Their theory was also incorrect in that it ascribed the barrier properties of the membrane to electrostatic repulsion from the protein layer rather than the energetic cost of crossing the hydrophobic core . A more direct investigation of the membrane was made possible through the use of electron microscopy in the late 1950s . After staining with heavy metal labels, Sjöstrand et al. noted two thin dark bands separated by a light region, which they incorrectly interpreted as a single molecular layer of protein . A more accurate interpretation was made by J. David Robertson, who determined that the dark electron - dense bands were the headgroups and associated proteins of two apposed lipid monolayers . In this body of work, Robertson put forward the concept of the "unit membrane ." This was the first time the bilayer structure had been universally assigned to all cell membranes as well as organelle membranes . </P> <P> The idea of a semipermeable membrane, a barrier that is permeable to solvent but impermeable to solute molecules was developed at about the same time . The term osmosis originated in 1827 and its importance to physiological phenomena realized, but it was not until 1877 when the botanist Pfeffer proposed the membrane theory of cell physiology . In this view, the cell was seen to be enclosed by a thin surface, the plasma membrane, and cell water and solutes such as a potassium ion existed in a physical state like that of a dilute solution . In 1889, Hamburger used hemolysis of erythrocytes to determine the permeability of various solutes . By measuring the time required for the cells to swell past their elastic limit, the rate at which solutes entered the cells could be estimated by the accompanying change in cell volume . He also found that there was an apparent nonsolvent volume of about 50% in red blood cells and later showed that this includes water of hydration in addition to the protein and other nonsolvent components of the cells . Overton (a distant cousin of Charles Darwin) first proposed the concept of a lipid (oil) plasma membrane in 1899 . The major weakness of the lipid membrane was the lack of an explanation of the high permeability to water, so Nathansohn (1904) proposed the mosaic theory . In this view, the membrane is not a pure lipid layer, but a mosaic of areas with lipid and areas with semipermeable gel . Ruhland refined the mosaic theory to include pores to allow additional passage of small molecules . Since membranes are generally less permeable to anions, Leonor Michaelis concluded that ions are adsorbed to the walls of the pores, changing the permeability of the pores to ions by electrostatic repulsion . Michaelis demonstrated the membrane potential (1926) and proposed that it was related to the distribution of ions across the membrane . Harvey and Danielli (1939) proposed a lipid bilayer membrane covered on each side with a layer of protein to account for measurements of surface tension . In 1941 Boyle & Conway showed that the membrane of resting frog muscle was permeable to both K+ and Cl -, but apparently not to Na+, so the idea of electrical charges in the pores was unnecessary since a single critical pore size would explain the permeability to K+, H+, and Cl - as well as the impermeability to Na+, Ca+, and Mg++ . </P> <P> With the development of radioactive tracers, it was shown that cells are not impermeable to Na+ . This was difficult to explain with the membrane barrier theory, so the sodium pump was proposed to continually remove Na+ as it permeates cells . This drove the concept that cells are in a state of dynamic equilibrium, constantly using energy to maintain ion gradients . In 1935, Karl Lohmann discovered ATP and its role as a source of energy for cells, so the concept of a metabolically - driven sodium pump was proposed . The tremendous success of Hodgkin, Huxley, and Katz in the development of the membrane theory of cellular membrane potentials, with differential equations that modeled the phenomena correctly, provided even more support for the membrane pump hypothesis . </P>

Who was the first to propose that cell membranes are phospholipid bilayers