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Cold Spring Harb. Physical chemistry of curvature and curvature stress in membranes. However, it was not until the s that works like those from Haydon and Taylor emphasized the dramatic role of thermodynamics to determine the structure of biological membranes [ ].
Even once the thermodynamic argument had entered the discussion of biological membranes, the first attempts to account for these constraints failed to fully assess their intensity. Hydrophobic and hydrophilic interactions were shown to rule the contact between lipids and proteins [ ], yet the early hypotheses often assumed that micellar mixes of lipids and proteins would have been the more stable structures [ ], thus favoring the subunit-based models.
A significant breakthrough was achieved when the study of membrane protein conformation became possible. The early paucimolecular model had depicted the coating proteins as globular [ ], but in the s the evolution of the model had led to the assumption that the proteins were unwrapped in a conformation similar to a beta sheet [ ]. In , several studies showed that the membrane proteins had an alpha or globular conformation rather than a beta structure [ - ].
The alpha helices were suggested to cross the membrane, thus providing a structural framework to the transmembrane proteins that had been predicted in the permeability and transport studies.
These works also acknowledged the importance of the thermodynamic constraints to determine the lipid-protein interactions and were especially influential because some of their authors, especially Singer, took part in the formulation of the current version of the fluid mosaic model. In and , Singer and Nicolson presented their fluid mosaic model of cell membrane structure.
The basics of the model have remained the same ever since: the membrane is a lipid bilayer with hydrophilic parts on the sides and hydrophobic parts in the interior; proteins can interact with the surface through transient polar contacts, but a lot of proteins are partially or totally embedded in the lipid bilayer where their hydrophobic parts also interact with the hydrophobic parts of lipids Figure 1.
In the light of the historical account on cell membrane discovery that I have reported, it is apparent that the success of the fluid mosaic model lay not so much in its originality as in its timeliness and scope: It accommodated most of the evidence available at its time and made predictions that would be demonstrated later.
On the one hand, the model was supported by evidence from different origins: 1 the permeability and transport studies that predicted enzyme-like transmembrane proteins [ ]; 2 the apparent lack of lipids to make up complete bilayers [ 94 ], thus pointing out to the participation of proteins in the membrane plane; 3 electron microscopy pictures, including freeze-etching studies that suggested the presence of proteins within the membranes [ ]; 4 the stability of artificial lipid bilayers that supported them as suitable and sufficient components to make up structures similar in the biological membranes [ ]; and 5 the favorable conformations predicted for the membrane proteins [ ].
On the other hand, the model was even more influential owing to the assumptions that it highlighted or newly predicted. First, as it was soundly established on thermodynamic grounds, the model enhanced the study of hydrophobic forces, which would subsequently become one of the major explanatory parameters to describe the biological macromolecules [ 2 ]. It is important to point out that, more than any generalization from biological observations—as was the case in the unit membrane, for example—the fact that the model is based in universal physico-chemical constraints is the most convincing argument for its general application in biology.
Moreover, the acknowledgement of the thermodynamic hydrophobic constraints improved our understanding of membrane proteins, which in turn significantly improved our picture of membranes [ 6 ]. Some dramatic landmarks in membrane protein depiction were the early resolution of the first tridimensional structure of a transmembrane protein the archaeal bacteriorhodopsin, [ ] ; the development of the patch-clamp technique, which allowed the understanding of single ion channels [ , ]; the discovery of the rotatory catalysis that allows the ATP synthesis by ATPases [ ]; and the late discovery of the aquaporins [ , ], which are water channels essential to understanding the water movements that have intrigued cell biologists for more than a century [ ].
Interestingly, now that our knowledge on membrane proteins has developed, the importance of lipid interaction for protein folding is becoming clearer and is still a promising line of research for the future [ , ].
Second, since this model is intrinsically fluid, it predicted that the distribution of most molecules in the lateral range would be essentially random, but it also suggested that specific clusters i. Although mainly ignored for some time, these microdomains have been the subject of intensive research in the last 20 years and the recent introduction of new techniques should continue to improve our understanding of interactions among membrane components [ , ].
Finally, the asymmetry of membranes has also proven to be a fruitful characteristic to explore. The idea that membranes had different components in the inner and outer sides of the membrane was not new, but this hypothesis was taken one step further because the model provided an explanation: The high, free energy of activation necessary for the hydrophilic part of a membrane component to cross the hydrophobic membrane core prevented the random tumbling [ 1 ].
Hence, the asymmetry which was already suspected for the oligosaccharides [ , ] was rapidly extended in the s to lipids, transmembrane proteins or peripheral proteins—for instance those related to the cytoskeleton [ , - ]. In summary, since its formulation in the s, the fluid mosaic model has been modernized to account for further observations, but it has barely been altered. It remains the most explanatory hypothesis to understand biological membranes.
Although the subject of cell membrane discovery could certainly be developed further, the information reviewed here should already be enough to point out the major limitations of the majority of previous, short historic accounts on this topic [ 5 - 7 , 9 , 10 , ].
These criticisms are not necessarily related to his well-known concept of scientific revolutions, but I will also briefly tackle the question in order to broaden the perspective of this review. Interestingly, the formulation of the modern fluid mosaic model has recently attracted some epistemological interest [ ]. This recent work suggested that the fluid mosaic model did not drive out its predecessor through a complete revision of available data in a Kuhnian sense; instead, it was the result of a synthesis effort between new pieces of evidence and different models.
According to this analysis, I think that if the history of the discovery of cell membranes can illustrate some dramatic change in perspective in biology, it should be the transition from the understanding of the cell as a colloid to the bounded, highly concentrated solution currently in use.
I think that this transition could be understood in Bachelardian terms as a discontinuity between the pre-scientific era of biology and modern science [ ]. Yet, it is not in the scope of this review to carry out a detailed epistemological analysis on the history of the Cell, so I will now move on to the other Kuhnian arguments that I think to be directly relevant to the critical analysis of the cell membrane historiography. When Kuhn tried to explain the difficulty in accounting for scientific revolutions, he made a particular case for the analysis of the sources of authority, i.
He criticized that most of these sources did not provide a comprehensive historical account of the actual events in the way they were understood at the time of their discovery. These texts instead presented individual experiments or thoughts that could be easily viewed as explanatory contributions to the current paradigm. Although these devices may be adequate for pedagogical purposes, such a presentation distorts the actual historical reconstruction.
The stake in this strategy is not only that it may contribute to hide a scientific revolution, as Kuhn feared, but also to make an inaccurate and oversimplified historiography become repeated and established. These inaccuracies have probably little impact on our current membrane research, but we should be aware of their existence in order to avoid perpetuating a historically questionable timeline.
I hope that this review will encourage other scholars to critically revise our short accounts on fields traditionally underrepresented in the History of Science studies as, for example, cell biology, microbiology and biochemistry. The historical analysis of the formulation of the current membrane model is not only relevant to those interested in membranes: it may also provide some lines of reflection on early evolution, the minimal cell concept, the origins of life and synthetic life.
All these subjects question our vision of the cell, and the membrane is arguably one of the most essential components of the unit of life concept. To begin with, we can step back to ask the question of the very necessity of the unit of life notion. It has been argued that the Cell Theory stands on the biological atomism, which postulated the existence of a basic indivisible unit of life well before any precise description of this unit could be made [ ].
According to this appealing analysis, the atomistic idea remained implicit along with the new discoveries that led to and established the Cell Theory. Determining the appropriateness of biological atomism is a deep epistemological question, which is not the matter here.
Yet, if we accept that the unit of life is a reality that we can study in spite of the diversity of opinions on the identity of this unit, the current preferred candidate for this position among biologists remains the Cell. Therefore, as all known cells are bounded by cell membranes, understanding the importance of these structures becomes crucial to our current definition of the unit of life. The historical analysis supports the progressive acknowledgement in the last decades of the importance of cell boundaries in the fields of early evolution and the origins of life [ - ]:.
As the unit of life, the cell entails some kind of identity that differentiates it from other cells and from the environment. Since it also has a composite structure, the cell requires a mechanism to keep all its components together.
Historically, two mechanisms have been envisioned: either all the components remain together because they establish direct interactions in a physical network the colloid chemistry or they are compartmentalized by some structure. It is important to remember that even after the discovery of the cell membrane, the colloid hypothesis survived many years and was only replaced when the biological macromolecules started to be analyzed as discrete structures. This is relevant to the origins of life, as well as synthetic life studies, because it supports current thinking that the compartmentalization is one of the very basic characteristics of any cell [ - ], no matter how primitive or minimal it may be.
The membrane embodies one of the main paradoxical characteristics of life: a cell is a system dependent on external compounds and energy to keep the differences that it maintains with the same environment where it gets its raw material. Although membranes were thought for a long time to be passive structures that just allowed solutes to diffuse across them, we now know that modern membranes are necessarily endowed with the ability to control the entry and exit of molecules depending on their needs, even sometimes against the chemical gradients.
According to this observation, it seems important to include a thought about active transport mechanisms in all works trying to describe the nascent life.
This does not mean that complicated structures, like proteins, had to be present from the very start of compartmentalization. For instance, transmembrane gradient formation based on membrane dynamics and alternative transporter molecules e. RNA molecules have been studied in recent years [ - ]. We can expect that the awareness of the importance of active transport for all cells will soon attract more attention to this fascinating subject from the researchers working on the origins of life.
Contrary to early assumptions about membranes, one of the major foundations upon which the fluid mosaic model is built is their ever-changing dynamic structure.
This allows modern membranes to constantly change their activities according to the requirements of the cell and it is likely that the same could have occurred in early membranes. Such a hint is promising because it could intersect with the increasing interest of the origins of life field in studying the changing abilities of membranes made up from mixed amphiphile solutions [ - ]. Finally, there are at least two fundamental aspects of membranes that have not been discussed in this review because their contribution to the understanding of membranes was low, but they cannot be neglected when referring to membrane contributions to cells.
These are the division of membranes and their role as transducers of messages from the environment. Although membrane division has already attracted some attention in the context of the origins of life [ ], very little is known about the interactions among early cells. Hopefully, both subjects will be further explored in the near future. I thank the reviewers for their comments. The manuscript has been revised twice taking into account their remarks. This manuscript by Jonathan Lombard provides a very thorough and detailed historical account of the evolution of the notion of cell boundaries over the years that spanned between the initial recognition that living organisms were comprised of cells, in the middle of the 17th century, and , with the advent of the fluid mosaic model, and the now generally accepted view that all living cells are surrounded by biological membranes made of lipid bilayers.
Although I am not competent to judge the accuracy of this historical report, and would not know if equivalent works have been published previously, I feel that this manuscript should represent a valuable addition to the field, and that the final parts of the manuscript, and the discussion in particular, raise several interesting questions and prospects.
All these good things being said, despite the tremendous amount of historical work which has clearly gone into assembling this manuscript, I must admit that I have found the reading of this manuscript to be rather cumbersome, and even very hard work for the early historical parts. I have communicated numerous corrections and editorial suggestions to the author directly, and hope that this will help him to produce a revised manuscript that will be easier to read, and thus more useful for the scientific community.
The overall structure of the new version of the manuscript has remained unchanged, but I have rewritten many paragraphs and shuffled some sections in order to clarify their message. I have also tried to make the transitions between paragraphs more fluent and I have removed redundant information to make more obvious the common thread of the text.
The new version of the paper has been checked by a professional journalist native in English who helped me to make the reading smoother. Thus, I think that the current version of the manuscript should be more easily readable than the first version. In this long paper, the author describes, in considerable detail, the history of biological membrane research, with an emphasis on the role of the membrane as the active cell boundary that determines what gets into or out of the cell and what remains inside or outside.
It is rather surprising to read, as a submission to a biology journal, an article that earnestly addresses the intricacies of the history of research in a particular field, without making much effort to formulate any new concept on the functions or evolution of membranes.
This is not a criticism, the history of concepts and misconceptions is useful and interesting in itself. What is missing, from my perspective, in this article, is any discussion of organellar and other intracellular membranes as well as membranes found in virions.
The intracellular membranes are indeed a fascinating subject of study and I would have been glad to introduce them in my review. Therefore, I have preferred to stick to the core of the subject, namely the origins of the membrane concept and the fluid mosaic model. As for other fields, I referred to intracellular membranes only when their study directly contributed to the storyline that I was trying to highlight in this paper. But I will consider the possibility of preparing a separate review about the history of intracellular membranes.
In order to account for the suggestions made by the third reviewer, the final section of the conclusion has been considerably changed. The review by Lombard is a nice survey on the evolution in understanding the nature of cell envelopes in the course of past three centuries.
It is an entertaining reading indeed and there is not much to comment. Introduction, line 31ff : The reader can get an impression that any lipid molecules tend to join into a membrane bilayer as the most thermodynamically stable structure. This is not the case. One of conditions of forming a bilayer is a match between the sizes of the hydrophobic and hydrophilic parts of the molecules involved [1].
If the hydrophilic head is larger, then the most stable structure is not a bilayer, but a micelle. It might be interesting to know whether they remained a historic curiosity or there is a historic connection with modern chemical engineering of nanoscale systems. I had never thought about precipitation membranes in the perspective of nanostructures. Unfortunately, I do not know anything about chemical engineering of nanoscale systems, and this would be a subject too distant from the rest of the review to be included in it.
But I appreciate the comment and I will keep it in mind for the future. While Singer, as it can be followed from his publications, was particularly interested in understanding the nature of biological membranes, Peter Mitchell was more interested in the processes of membrane transport and mechanisms of energy conversion.
Thereby Mitchell - and his colleagues - needed implicitly some working model of a biological membrane. Thereby Mitchell did not make any statements on the nature of biological membranes. Furthermore, the very fact that chemically quite different, small proton-carrying molecules could uncouple oxidative phosphorylation by diffusing across membrane bilayer as shown first by Skulachev and co-workers [4], this reference should be included , implies the presence of free lipid patches accessible from the water phase for these small molecules; it is across such patches that the uncoupling molecules could diffuse.
Again, Skulachev and co-workers did not discuss the presence of these free patches because they were interested in understanding the mechanism of energy conversion.
Still, their working model of the membrane should have been that of a mosaic membrane. However, the studies of energy conversion did not provide - at least at that time - any information on the lateral motility of proteins in the membrane. It is not incidental that the paper of Singer and Nicolson [5], in addition to an extended analysis of literature data, also provided experimental evidence of the protein mobility in native membranes. This was the truly new piece of evidence that helped to compile a whole picture of a fluid, mosaic membrane.
Their work certainly influenced the way membranes were considered, but it was not used as a piece of evidence to directly oppose the predominant paucimolecular model. The citation to Skulachev and colleagues has been included in the new version of the manuscript.
Thomas Kuhn has developed his theory based on the history of physics, therefore his model does not work as nicely with less exact subjects. This kind of development can be hardly imagined in physics. I would suggest skipping or modifying this section. Apparently the message was not clear enough in the first version of the paper, so I have modified the text to emphasize more this point.
This does not imply that early membranes had to have a developed protein apparatus for selective transport, but whatever the nature of the specific transporters present in the primordial cells, their functions are arguably very ancient. From my opinion, several different subjects are mixed up in this passage. They deserve being sorted out. The very fact that proteins and lipids diffuse within the liquid matrix of the bilayer means that biological membranes are dynamic.
As far as I know, the dynamic nature of biological membrane has not been challenged neither by authors of the mentioned references and [7, 8]. The apparent usage of dynamic and active as interchangeable terms by the author makes this passage even more confusing. The models in the mentioned references and [7, 8], which are accused in implying passive membranes, in fact, build on an assumption that the very first membranes could be impermeable to large polymeric molecules but leaky to small molecules.
This vision of primordial membranes is not quite original and could be traced to the studies of Deamer, Luisi, Szostak, Ourisson, Nakatani and their co-workers [].
These authors argued that abiotically formed amphiphilic molecules, most likely, fatty acids of phosphorylated, branched polyprenol-like compounds [10, 12, 14, 18, 19], which may have enveloped the first cells, could not be as sophisticated as modern two-tail lipids. Vesicles formed from such molecules are million times more leaky that vesicles from modern, two-tail lipids [18].
Hence, such vesicles could trap large polymers but not small molecules and ions. This leakiness, however, could have been a key advantage. In turn, this would favor the development of systems that could trap small molecules by attaching them to intracellular polymers - and thus preventing their escape.
Hence, leaky membranes could have driven the emergence of different polymerases, including the translation system. The feasibility of such a mechanism has been experimentally shown [13].
Accordingly, even the first abiotically formed membranes mentioned in [7, 8] should have been both dynamic and active according to Lombard. The leakiness to ions per se neither makes a cell membrane passive nor obligatory kills the cell. Even a leaky membrane will faithfully maintain all disequilibria that concern large polymeric molecules.
Modern cells are quite robust concerning the tightness of their membranes. In a previous version of this manuscript, I used both terms indistinctly to refer to what should only be considered as active transport. Although I had found the reading of the initial version of this manuscript to be rather cumbersome, I must say that I am impressed by how improved and easier to read the revised version has become, and I am now confident that it represents a very useful addition to the scientific literature.
I have no further comment and believe that the paper is ready for publication. For instance, recent works have shown that transmembrane gradients across lipid bilayers could spontaneously arise in prebiotic conditions [,]. It has even been argued that RNA molecules could have acted as transporters [ , ]. From this wording, the reader can get an impression that refs.
However, this is not the case. Such a difference could not arise spontaneously, i. Accordingly refs. The ref. And, finally, the ref. However, Chen and Szostak themselves emphasized that the formation of the proton gradient was driven by thermodynamically favorable incorporation of the new hydrophobic fatty acid molecules into the membranes of the vesicles. Hence, the formation of the proton gradient was not spontaneous. Chen and Szostak observed the formation of the transmembrane pH difference under very special conditions where polar, charged, and bulky arginine molecules were used as the only cations in the medium.
The seminal article of Chen and Szostak, in fact, shows that:. To summarize, the author of the review fails to provide any experimental evidence of a spontaneous formation of transmembrane gradients across primitive lipid bilayers in prebiotic conditions. I thank the reviewer for his careful lecture of the article. I did not mean this part of the paper to be as controversial as the reviewer seems to find it to be. The main objective of my review is to provide a new survey on the history of the discovery of cell membranes.
I think that this subject is even more exciting when it is placed in the context of modern debates about early membranes. But the issue of early membranes is a wide and hot topic and this review is not the place to discuss it into detail. This review was never intended to provide experimental data about transmembrane gradient formation in early membranes. I hope that the reviewer will find these changes satisfactory.
I request explicitly that my comments to the manuscript should be published together with the complete reference list [that I provided]. Q Rev Biophys , 13 2 — Mitchell P: A general theory of membrane transport from studies of bacteria. Nature , — Lenard J, Singer SJ: Protein conformation in cell membrane preparations as studied by optical rotatory dispersion and circular dichroism.
Science , — Szathmary E: Coevolution of metabolic networks and membranes: the scenario of progressive sequestration. Deamer DW: The first living systems: a bioenergetic perspective. Microbiol Mol Biol Rev , 61 2 — Deamer DW: Origins of life: How leaky were primitive cells?
Orig Life Evol Biosph , 42 5 — Chem Biol , 14 3 — Ourisson G, Nakatani Y: The terpenoid theory of the origin of cellular life: the evolution of terpenoids to cholesterol. Chem Biol , 1 1 — Chem Biodivers , 4 5 — Mansy SS: Membrane transport in primitive cells.
Cold Spring Harb Perspect Biol , 2 8 :a Trends Biochem Sci , 34 4 — Cell , 7 — Orig Life Evol Biosph , 35 2 — RNA , 10 10 — Trends Genet , 21 12 — I thank D. Moreira, M. Morange, P. Capy, S. Gribaldo, V. Daubin and O. Lespinet for their encouragements to publish this work. I also thank D. Petitjean, D. Duncan, two previous anonymous referees and the three reviewers from Biology Direct for their comments on the manuscript. Competing interests. JL is responsible for the conception of the review, the bibliographic analysis and the manuscript.
National Center for Biotechnology Information , U. Journal List Biol Direct v. Biol Direct. Published online Dec Jonathan Lombard. Author information Article notes Copyright and License information Disclaimer.
National Evolutionary Synthesis Center, W. Jonathan Lombard, Email: moc. Corresponding author. Received Jul 11; Accepted Dec 3. This article has been cited by other articles in PMC.
Abstract Abstract All modern cells are bounded by cell membranes best described by the fluid mosaic model. Reviewers This article was reviewed by Dr. Introduction Modern descriptions of the cell are intimately related to the notion of cell membranes. Open in a separate window. Figure 1. Review In the next sections, I will review the main discoveries that led to our current model of biological membranes: 1 the long path from the original assumptions about cell boundaries in the early Cell Theory to the first evidence that supported the existence of membranes; 2 early studies on cell membrane structure; 3 how evidence from permeability studies progressively built an alternative vision of cell boundaries—distinct from the model favored in the field of membrane studies; and 4 how the fluid mosaic model came into being.
Figure 2. Figure 3. A time before the cell membrane It is surprising to note that most short accounts of cell membrane discovery barely discuss the early controversies on the existence of membranes around the cells [ 5 - 10 ]. The cell walls at the time of the cell theory proposal The construction of the cell concept was a complex process that spanned the work of a large number of naturalists from the XVII th to the XIX th centuries [ 11 , 12 ]. Figure 4. Cells without membranes The second half of the XIX th century was a period of many fascinating biological debates and discoveries related to the Darwinian evolution, the physiology of both animal and plants and, even in histology, the discovery of mitosis.
Early osmotic studies and the cell boundaries Osmosis studies orange boxes in Figure 2 had an ambiguous relationship with the early understanding of cell membranes. Later osmotic studies and artificial membranes In , Von Mohl treated plant tissues with alcohol and different acids and described the detachment of the protoplasm from the interior of the cell walls.
Figure 5. Late membrane-less hypotheses As it has been shown so far, during most of the XIX th century, cell membranes attracted limited attention and the dominant opinion was that cell membranes often mistaken for cell walls were secondary structures that resulted from the contact between the protoplasmic colloid and the environment.
The birth of cell membranes The existence of cell membranes did not become popular until the turn of the XX th century. The permeability of molecules according to their polarity In the s, two confronting views competed each other to explain how semipermeable membranes operated: Traube had suggested that precipitation membranes had small pores that allowed them to behave like sieves, whereas Nernst introduced the idea that permeating substances were those that could dissolve in the membranes [ 59 , 64 , 65 ].
The electrophysiology of excitable cells The electrophysiology is a domain unto itself, so here I will only briefly summarize the main indirect contributions to the field of cell membranes at the turn of the XX th century purple boxes in Figure 2. The first membrane structures In the previous section, I have shown that many authors in the XIX th century thought that membranes were not essential parts of cells and even those who recognized their importance did not conceive membranes as we do today.
Gorter and Grendel: a relative breakthrough In the early XX th century it appeared clear that, if cell membranes existed, they would likely be at least partially lipid-based.
Figure 6. Figure 7. First direct studies on membrane structure The formulation of the lipid bilayer hypothesis had opened the door to the molecular description of cell membrane structure. Figure 8. Contemporary competitors: the mosaic models Despite of the prevalence of the paucimolecular model in the mid-XX th century, this hypothesis was not devoid of competitors.
Figure 9. A phospholipid molecule consists of a three-carbon glycerol backbone with two fatty acid molecules attached to carbons 1 and 2, and a phosphate-containing group attached to the third carbon. This arrangement gives the overall molecule an area described as its head the phosphate-containing group , which has a polar character or negative charge, and an area called the tail the fatty acids , which has no charge. They interact with other non-polar molecules in chemical reactions, but generally do not interact with polar molecules.
When placed in water, hydrophobic molecules tend to form a ball or cluster. The hydrophilic regions of the phospholipids tend to form hydrogen bonds with water and other polar molecules on both the exterior and interior of the cell. Thus, the membrane surfaces that face the interior and exterior of the cell are hydrophilic. In contrast, the middle of the cell membrane is hydrophobic and will not interact with water.
Therefore, phospholipids form an excellent lipid bilayer cell membrane that separates fluid within the cell from the fluid outside of the cell. Phospholipid aggregation : In an aqueous solution, phospholipids tend to arrange themselves with their polar heads facing outward and their hydrophobic tails facing inward. The structure of a phospholipid molecule : This phospholipid molecule is composed of a hydrophilic head and two hydrophobic tails.
The hydrophilic head group consists of a phosphate-containing group attached to a glycerol molecule. The hydrophobic tails, each containing either a saturated or an unsaturated fatty acid, are long hydrocarbon chains. Proteins make up the second major component of plasma membranes. Integral proteins some specialized types are called integrins are, as their name suggests, integrated completely into the membrane structure, and their hydrophobic membrane-spanning regions interact with the hydrophobic region of the the phospholipid bilayer.
Single-pass integral membrane proteins usually have a hydrophobic transmembrane segment that consists of 20—25 amino acids. Some span only part of the membrane—associating with a single layer—while others stretch from one side of the membrane to the other, and are exposed on either side. Some complex proteins are composed of up to 12 segments of a single protein, which are extensively folded and embedded in the membrane.
This type of protein has a hydrophilic region or regions, and one or several mildly hydrophobic regions. This arrangement of regions of the protein tends to orient the protein alongside the phospholipids, with the hydrophobic region of the protein adjacent to the tails of the phospholipids and the hydrophilic region or regions of the protein protruding from the membrane and in contact with the cytosol or extracellular fluid.
Structure of integral membrane proteins : Integral membrane proteins may have one or more alpha-helices that span the membrane examples 1 and 2 , or they may have beta-sheets that span the membrane example 3. Carbohydrates are the third major component of plasma membranes. They are always found on the exterior surface of cells and are bound either to proteins forming glycoproteins or to lipids forming glycolipids.
These carbohydrate chains may consist of 2—60 monosaccharide units and can be either straight or branched.
Along with peripheral proteins, carbohydrates form specialized sites on the cell surface that allow cells to recognize each other. Similar types of glycoproteins and glycolipids are found on the surfaces of viruses and may change frequently, preventing immune cells from recognizing and attacking them.
The glycocalyx is highly hydrophilic and attracts large amounts of water to the surface of the cell. The mosaic nature of the membrane, its phospholipid chemistry, and the presence of cholesterol contribute to membrane fluidity.
There are multiple factors that lead to membrane fluidity. First, the mosaic characteristic of the membrane helps the plasma membrane remain fluid. The integral proteins and lipids exist in the membrane as separate but loosely-attached molecules. The membrane is not like a balloon that can expand and contract; rather, it is fairly rigid and can burst if penetrated or if a cell takes in too much water. However, because of its mosaic nature, a very fine needle can easily penetrate a plasma membrane without causing it to burst; the membrane will flow and self-seal when the needle is extracted.
Membrane Fluidity : The plasma membrane is a fluid combination of phospholipids, cholesterol, and proteins. The second factor that leads to fluidity is the nature of the phospholipids themselves.
In their saturated form, the fatty acids in phospholipid tails are saturated with bound hydrogen atoms; there are no double bonds between adjacent carbon atoms.
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