Editing Cell theory (section)

== Opposing concepts ==

The cell was  first discovered by Robert Hooke in 1665 using a microscope. The first cell theory is credited to the work of [[Theodor Schwann]] and [[Matthias Jakob Schleiden]] in the 1830s. In this theory the internal contents of cells were called [[protoplasm]] and described as a jelly-like substance, sometimes called living jelly. At about the same time, [[colloidal chemistry]] began its development, and the concepts of [[bound water]] emerged. A [[colloid]] being something between a [[Solution (chemistry)|solution]] and a [[Suspension (chemistry)|suspension]], where [[Brownian motion]] is sufficient to prevent [[sedimentation]].{{citation needed|date=September 2023}}
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 wasn’t until 1877, when the [[botanist]] [[Pfeffer]] proposed the [[History of cell membrane theory|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.{{citation needed|date=September 2023}}

=== Membrane and bulk phase theories ===

Two opposing concepts developed within the context of studies on [[osmosis]], permeability, and electrical properties of cells.<ref>{{cite book|last=Ling|first=Gilbert N.|title=In search of the physical basis of life|date=1984|publisher=Plenum Press|location=New York|isbn=0306414090}}</ref> The first held that these properties all belonged to the plasma membrane whereas the other predominant view was that the [[protoplasm]] was responsible for these properties. The [[History of cell membrane theory|membrane theory]] developed as a succession of ad-hoc additions and changes to the theory to overcome experimental hurdles. 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.<ref>{{Cite journal|last1=Michaelis|first1=L.|title=Contribution to the Theory of Permeability of Membranes for Electrolytes|journal=The Journal of General Physiology|volume=8|issue=2 |pages=33–59|year=1925|pmid=19872189|pmc=2140746|doi=10.1085/jgp.8.2.33}}</ref>

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 and Conway showed that the membrane of frog muscle was permeable to both {{chem|K|+}} and {{chem|Cl|-}}, but apparently not to {{chem|Na|+}}, so the idea of electrical charges in the pores was unnecessary since a single critical pore size would explain the permeability to {{chem|K|+}}, {{chem|H|+}}, and {{chem|Cl|-}} as well as the impermeability to {{chem|Na|+}}, {{chem|Ca|+}}, and {{chem|Mg|2+}}.
Over the same time period, it was shown (Procter and Wilson, 1916) that gels, which do not have a semipermeable membrane, would swell in dilute solutions.{{citation needed|date=September 2023}}

[[Jacques Loeb]] (1920) also studied [[gelatin]] extensively, with and without a membrane, showing that more of the properties attributed to the plasma membrane could be duplicated in [[gels]] without a membrane. In particular, he found that an electrical potential difference between the gelatin and the outside medium could be developed, based on the {{chem|H|+}} concentration. Some criticisms of the membrane theory developed in the 1930s, based on observations such as the ability of some cells to swell and increase their surface area by a factor of 1000. A lipid layer cannot stretch to that extent without becoming a patchwork (thereby losing its barrier properties). Such criticisms stimulated continued studies on protoplasm as the principal agent determining cell permeability properties.{{citation needed|date=September 2023}}

In 1938, Fischer and Suer proposed that water in the protoplasm is not free but in a chemically combined form—the protoplasm represents a combination of protein, salt and water—and demonstrated the basic similarity between swelling in living tissues and the swelling of gelatin and [[fibrin]] gels. Dimitri Nasonov (1944) viewed proteins as the central components responsible for many properties of the cell, including electrical properties.
By the 1940s, the bulk phase theories were not as well developed as the membrane theories. In 1941, Brooks and Brooks published a monograph, "The Permeability of Living Cells", which rejects the bulk phase theories.{{citation needed|date=September 2023}}

===Steady-state membrane pump concept ===

With the development of [[radioactive tracers]], it was shown that cells are not impermeable to {{chem|Na|+}}. This was difficult to explain with the membrane barrier theory, so the sodium pump was proposed to continually remove {{chem|Na|+}} as it permeates cells. This drove the concept that cells are in a state of [[dynamic equilibrium]], constantly using energy to maintain [[ion gradient]]s. In 1935, {{ill|Karl Lohmann (chemist)|de|Karl Lohmann (Biochemiker)|lt=Karl Lohmann}} discovered [[Adenosine triphosphate|ATP]] and its role as a source of energy for cells, so the concept of a metabolically-driven [[sodium pump]] was proposed.{{citation needed|date=September 2023}}
The success of [[Alan Lloyd Hodgkin|Hodgkin]], [[Andrew Huxley|Huxley]], and [[Bernard Katz|Katz]] in the development of the membrane theory of cellular membrane potentials, with differential equations that modeled the phenomena correctly, provided further support for the membrane pump hypothesis.{{citation needed|date=September 2023}}
 
The modern view of the plasma membrane is of a fluid lipid bilayer that has protein components embedded within it. The structure of the membrane is now known in great detail, including 3D models of many of the hundreds of different proteins that are bound to the membrane.
These major developments in cell physiology placed the membrane theory in a position of dominance and stimulated the imagination of most physiologists, who now apparently accept the theory as fact—there are, however, a few dissenters.{{citation needed|date=March 2020}}

=== Reemergence of bulk phase theories ===

In 1956, Afanasy S. Troshin published a book, ''The Problems of Cell Permeability'', in Russian, in which he showed that permeability was of secondary importance in determining the patterns of equilibrium between the cell and its environment. Troshin showed that cell water decreased in solutions of galactose or urea although these compounds did slowly permeate cells. Since the membrane theory requires an impermanent solute to sustain cell shrinkage, these experiments cast doubt on the theory. Others questioned whether the cell has enough energy to sustain the sodium/potassium pump. Such questions became even more urgent as dozens of new metabolic pumps were added as new chemical gradients were discovered.{{citation needed|date=September 2023}}

In 1962, [[Gilbert Ling]] became the champion of the bulk phase theories and proposed his association-induction hypothesis of living cells.<ref>{{Cite journal |last=Ling |first=Gilbert |date=2007 |title=Nano-protoplasm: the ultimate unit of life |url=https://pubmed.ncbi.nlm.nih.gov/19256352/ |journal=Physiological Chemistry and Physics and Medical NMR |volume=39 |issue=2 |pages=111–234 |issn=0748-6642 |pmid=19256352}}</ref><ref>{{Cite journal |last1=Ling |first1=G. N. |last2=Ochsenfeld |first2=M. M. |date=1965 |title=Studies on the ionic permeability of muscle cells and their models |journal=Biophysical Journal |volume=5 |issue=6 |pages=777–807 |doi=10.1016/S0006-3495(65)86752-2 |issn=0006-3495 |pmc=1367903 |pmid=5884012}}</ref><ref>{{Cite book |last=Ling |first=Gilbert Ning |url=https://books.google.com/books?id=nr3PAAAAMAAJ |title=A Physical Theory of the Living State: The Association-induction Hypothesis |publisher=Blaisdell Publishing Company |year=1962 |language=en}}</ref>