THEORY OF MEMBRANE FOLDING - BIOLOGY - 2025

The membrane folding theory proposes that the organelle membranes originated from the expansion and invagination of the plasma membrane. JD Robertson, a pioneer in electron microscopy, noted in 1962 that several intracellular bodies possessed a structure that was visually identical to the plasma membrane.

The idea of ​​a structure that delimits cells arose immediately after the concept of "cell" emerged, so several studies were carried out to elucidate the characteristics of this structure.

Plasma membrane

The plasma membrane

The plasma membrane is a structure formed by a double layer of phospholipids organized in such a way that the polar groups are oriented towards the cytosol and the extracellular medium, while the apolar groups are organized towards the interior of the membrane.

Its main function is to define cells, both eukaryotic and prokaryotic, since it physically separates the cytoplasm from the extracellular environment.

Despite its structural function, it is well known that the membrane is not static, but rather an elastic and dynamic barrier where a large number of essential processes for the cell occur.

Some processes that take place in the membrane are cytoskeletal anchoring, molecule transport, signaling, and connection with other cells to form tissues. In addition, a great variety of organelles also have a membrane in which other processes of great importance occur.

Background of the membrane folding theory

Electrophysiological studies

Long before Robertson came to propose the theory of membrane folding in 1962, studies were first carried out to determine what this structure looked like. In the absence of the electron microscope, electrophysiological studies predominated, among which the following stand out:

1895

Overton noted that lipids crossed the cell membrane more easily than molecules of another nature, therefore, he inferred that the membrane must be composed, for the most part, of lipids.

1902

J. Bernstein presented his hypothesis, which mentioned that the cells consisted of a solution with free ions delimited by a thin layer impermeable to these charged molecules.

1923

Fricke measured the ability of the erythrocyte membrane to store charges (capacitance), determining that this value was 0.81 µF / cm ².

Later it was determined that the membranes of other cell types had similar capacitance values, therefore, the membrane should be a unitary structure.

1925

Gorter and Grendel measured the area of ​​mammalian erythrocytes with the help of a microscope. They then extracted the lipids from a known number of this cell type and measured the area they occupied.

They obtained a 1: 2 cell: membrane ratio as a result. This meant that the cell membrane was a double structure, thus giving rise to the term “lipid bilayer”.

1935

Studies prior to 1935 suggested the presence of proteins in the membrane, this led Danielli and Davson to propose the Sandwich model or Protein-Lipid-Protein model.

According to this model, the plasma membrane consists of two layers of phospholipids that are found between two layers of proteins, which are associated with the membrane through electrostatic interactions.

Electron microscopy studies

In 1959, thanks to the appearance of electron microscopy, J. David Robertson collected enough evidence to confirm and complement the models proposed by Gorter and Grendel (1925) and Danielli and Davson (1935), and to propose the “Unitary Membrane” model.

This model retains the characteristic of the model proposed by Danielli and Davson of the lipid bilayer, with the variation of the protein layer which, in this case, is asymmetric and discontinuous.

What is membrane folding theory about?

The arrival of electron microscopy allowed us to have a fairly clear idea about how the plasma membrane was formed.

However, this fact was accompanied by the visualization of multiple intracytoplasmic membranes forming intracellular compartments, which led Robertson in 1962 to propose the "Theory of membrane folding".

The theory of membrane folding is that the plasma membrane increased its surface and was invaginated to give rise to intracytoplasmic membranes, these membranes surrounded molecules that were in the cytosol, thus originating organelles.

According to this theory, the nuclear envelope, the endoplasmic reticulum, the Golgi apparatus, lysosomes and vacuoles could have originated in this way.

The continuity that exists between the plasma membrane and the first three organelles mentioned above has been confirmed by electron microscopy studies in different cell types.

However, Robertson also proposed in his theory that vesicular organelles such as lysosomes and vacuoles also originated by invaginations that subsequently separated from the membrane.

Due to the characteristics of the membrane folding theory, it is considered as an extension of the unit membrane model that he himself proposed in 1959.

The micrographs taken by Robertson show that all of these membranes are the same and therefore should have a fairly similar composition.

However, the specialization of the organelles considerably modifies the composition of the membranes, which reduces the properties they have in common at the biochemical and molecular level.

Similarly, the fact that the membranes have as their main function is to serve as a stable barrier for aqueous media is maintained.

Importance of this theory

Thanks to all the tests carried out between 1895 and 1965, especially the microscopy studies carried out by JD Robertson, the importance of cell membranes was emphasized.

From its unitary model, the essential role that the membrane plays in the structure and function of cells began to be highlighted, to such an extent that the study of this structure is considered a fundamental issue in current biology.

Now, with respect to the contribution of membrane folding theory, this is not currently accepted. However, at the time, it led to more experts in the area trying to elucidate the origin not only of cell membranes, but also the origin of the eukaryotic cell itself, as Lynn Margulis did in 1967 when raising the endosymbiotic theory.

References

1. Lodish H, Berk A, Kaiser C, et al. Molecular Cell Biology. Vol 39. 8th ed.; 2008.
2. Heuser JE. In Memory of J. David Robertson. Am Soc Cell Biol. 1995: 11-13. Taken from heuserlab.wustl.edu.
3. Lee A. Membrane structure. Curr Biol. 2001; 11 (20): R811-R814. doi: 10.1083 / jcb.91.3.189s.
4. Gupta GP. Plant Cell Biology. Discovery Publishing House; 2004. Taken from books.google.
5. Heimburg T. Membranes-An Introduction. Therm Biophys Membr. 2007; (2001): 1-13. doi: 10.1002 / 9783527611591.ch1.
6. Stoeckenius W, Stoeckenius W, Engelman DM, Engelman DM. Review current models for the structure of biological membranes. J Cell Biol.