Biology Essay On Cells

We were finishing dinner at a conference on evolutionary developmental biology when a graduate student asked me to explain some comments I’d made during a question and answer session. I had disagreed with a colleague’s reliance on citation analysis to present a history of evolutionary developmental biology. Citation lists are political documents, I had argued. Citations don’t reveal whether a paper had influenced the author, or even whether the author had read it. Furthermore, a history of a new field should explain why the field arose. It might even have a mythos, a narrative theme for its origin story.

The student asked if my account of the history of evolutionary developmental biology had an underlying narrative and, if so, what it was. I told him something like, “Yes. If you analyze my accounts, you’ll find that there is an underlying narrative, and that narrative is ‘the return of the rightful sovereign.’ Development was originally seen as the motor of evolution, and the principal way of explaining evolution was through embryology. In fact, in the late 1800s, the word ‘evolution’ could mean either phylogenetic or embryological development. But genetics arose out of embryology, and eventually, evolution came to be seen as a proper subset of population genetics. Genetics displaced development as the way to study evolution. In my narrative, evo-devo represents the return of developmental biology to its rightful place as the means to study evolution.”

Sensing he didn’t get the connection, I continued. “The return of the rightful sovereign. Remember Errol Flynn’s Robin Hood, in which the captured monk dramatically sheds his clerical garb to reveal himself as King Richard, returned to England to correct John’s injustices?”

My dated allusion was not getting through, either. “Game of Thrones,” I hazarded.

“Yes!” he exclaimed, “I get it. Evo-Devo and Game of Thrones!”

As I recalled my version of developmental biology’s origin story, I pondered a larger question, which others had also noted [1]: Why and how has developmental biology, once a central focus of biology, been marginalized in our curriculum? Nobel Prizes and other awards for discoveries in developmental biology are often cast (even in scientific journals) as breakthroughs in genetics or in stem cell biology. Journal articles pertaining directly to developmental biology are often catalogued under “cancer biology,” “evolution,” or “neurobiology.” Developmental biology has even been disparaged as “old fashioned” by experts in the field who are doing it excellently, but who prefer to call it something else. In the most recent meeting of the Society for Developmental Biology, the president of the society, Blanche Capel [2], asked in her presidential address, “Did you ever think, like me, that Developmental Biology does not get the credit it deserves for its contributions to understanding the natural world?”

As should be clear by now, I have indeed wondered why developmental biology has been overlooked and am playing with a hypothesis to explain why. I propose that developmental biology (and its parent discipline, embryology) has been the stem cell of biological disciplines. It is not a “differentiated” discipline, but the pluripotent discipline that generates disciplines like genetics and immunology, all the while retaining its own identity.

(Developmental biology, it should be noted, is a twice-named discipline. In the 1950s, the term was coined by Paul Weiss and N. J. Berrill to include the parent discipline, embryology, as well as the study of adult stem cells and nonembryonic development, such as budding and regeneration. This was the impetus for the journal Developmental Biology. It was named again in the 1970s, for the annual series, Current Topics in Developmental Biology, where it was seen as the molecular approach to embryology. In both cases, “developmental biology” was viewed as the modernization and extension of embryology [3].)

So, let us begin with the cell theory. In the mid-1800s, the study of embryos gave rise to various theories of cell formation. Schleiden, Schwann, and Remak formed their cell theories to answer the question of how multicellular embryos emerged, and thus gave rise to the discipline of cytology/cell biology [4–6]. Today’s cell theory is largely based on the 1862 hypothesis of Robert Remak [7], who first figured out that the embryo is constructed by cell division and that all the cells of the body are descendants of the zygote. But where do these cells form? By the turn of that century, Eli Metchnikoff and other embryologists, looking for the sources and roles of the mesoderm (the middle cell layer of embryonic embryo), formulated the first approaches to immunology. Metchnikoff had found that the mesodermal cells of the starfish embryo budded off from the gut-producing endoderm and were capable of their own intracellular digestion, phagocytizing foreign bodies inserted into the larvae. His discovery led to the first hypotheses of cellular immunity [8]. Thus, by 1900, embryology had already given rise to cell biology and immunology.

Shortly thereafter, the gene theory was constructed by embryologists who had been embroiled in debates over what part of the embryo—the nucleus or the cytoplasm—controlled development. In the early 1900s, embryologists Theodor Boveri and E. B. Wilson believed that the nucleus, especially the nuclear chromosomes, carried the instructions for organismal development. In contrast, embryologist Thomas Hunt Morgan (who had written a monograph on the embryology of the frog egg) favored the cytoplasm [9]. By 1915, Morgan [10] inadvertently obtained the evidence that chromosomal genes were necessary for the production of inherited traits. (He had hoped to prove otherwise). Another embryologist, William Bateson, would later call this new field “genetics,” and Morgan [11] would formally separate the two fields, saying that genetics studied the transmission of inherited traits, whereas embryology studied their expression. While earlier genetics (the “assortment” phase) had been suggested by breeders such as Mendel, the field we now know as genetics (studying traits whose segregation and assortment can be explained by the locations of specific genes on particular chromosomes) came from the chromosomal studies of embryologists such as Morgan and Wilson, supplemented by the theoretical discussions and analyses of embryologist Theodor Boveri and Wilson’s graduate student, Walter Sutton.

As a student of both biology and religion in college, it struck me how the rise and separation of genetics from embryology, and the disparagement of the parent discipline by some of the acolytes of the new discipline, echoed the supersessionist rhetoric of Christianity as it separated from Judaism. Even more interestingly, some of the founders and critics of early genetics seemed to think so, too [12]. Morgan claimed that while geneticists kept the faith, embryologists had “run after false gods” [13]. Genetics was to replace embryology. There were many reasons for the dominance of genetics during the 20th century, not the least of which were the destruction of the Continental European laboratories during the two World Wars and the fear of mutations caused by the detonation and testing of atomic bombs [14,15].

As English replaced German as the language of science, so genetics replaced physiology and development, including theories of development as the motor of evolution. Early evolutionary theories, such as those of Robert Chambers and Charles Darwin’s grandfather, Erasmus, were based on embryonic development, especially developmental morphology. Chamber’s sensational and widely selling Vestiges of the Natural History of Creation was the first book “to link a developmental view of the world with evolution” [16]. Using von Baer’s principles of development, Chambers [17] argued that animal biodiversity was caused by alterations of embryonic development. In fact, Darwin explicitly viewed plant biodiversity as being predicated by alterations of floral development [18]. He also noted that natural selection could not produce the variations that provided the raw material for natural selection [18–20]. When Darwin’s theory was published, his contemporaries assumed that development was the motor that generated the variations that could be selected. Darwin’s continental champion, Ernst Haeckel [21] made embryology the key to phylogeny, and Darwin’s aggressive British champion, Thomas Huxley, wrote to Darwin that the differences between species could be traced back to the modifications of development. Evolutionary biologists such as Huxley and Herbert Spencer were greatly influenced by embryologist K. E. von Baer’s theories of development [22,23]. Indeed, when Huxley was writing [24], the word “evolution” could be used for both the individual or the species.

That view shifted with the advent of genetics. Rather than viewing evolutionary biology as the study of macroevolution, Morgan [11,25,26] would claim that only the study of intraspecies genetics was the “scientific” approach to evolution and that anything else (embryology and paleontology, to be sure) was “unscientific” and “philosophical.” He and his students carried the day (except in Russia, which viewed genetics as bourgeois metaphysics and retained an embryological view of evolution). In 1959, the centenary of Darwin’s volume, the Genetics Society of America undertook a public relations campaign to promulgate the message that Darwinism was correct because it could be fully explained by genetics. This was important because it would quiet both the Creationists in America and those scientists who favored Lysenko, the leader of Soviet biology, who embraced a Lamarckian theory of acquired heritability [27]. Embryology had given rise to the first mechanistic theories of evolution, only to be usurped by its rebellious child, genetics. Evolutionary developmental biology is now emphasizing that the emergence of new phenotypes occurs during embryonic development, and that developmental regulatory genes are crucial for evolution. Evolutionary biology cannot explain evolution by population genetics, alone. Knowledge of development is critical in explaining the origins of species. And this, as I explained to the graduate student, is the return of the rightful sovereign.

Neurobiology similarly has an embryological pedigree, and in the early 1900s, one of its biggest concerns was whether the axon was really a cellular process that extended meters in the body. Ross Granville Harrison’s inaugural tissue culture experiments [28] solved the problem by showing that the developing frog soma extended an enormous neurite. He and others also demonstrated signaling’s role in completing synapse formation and mediating the embryonic cues that guide axons from the original cell to its destined target. Through these studies of neural development, Harrison solved the problem that had so perplexed Ramón y Cajal and others who had sought to explain the patterns of neural connections in the adult body [29,30].

In 1859, the same year Darwin’s On the Origin of Species was published, Rudolf Virchow’s classic volume, Cellular Pathology, drew on embryology to explain pathology. Cancers, he argued, should be studied as errors of development because tumors appeared “by the same law, which regulated embryonic development” [31]. In the 1920s and 1930s, those embryonic laws were beginning to be explained by morphogenetic fields, and as early as 1935, C. H. Waddington [32] claimed that cancers could be studied as derangements of morphological fields established in the embryo. Tumors were seen as recapitulations of or truncated stages of normal development, and oncology emerged from the work of developmental biologists studying how misregulation leads to aberrant growth. During the mid-to-late 20th century, there was a fascinating reciprocal interaction between the two disciplines, as developmental biology provided mechanisms for cancer growth and cancer biology became a niche in which developmental biology could be nourished (i.e., get funding) [33,34]. Scientists such as T. Boveri, G. B. Pierce, and R. Auerbach used embryological means to study tumors and used tumors to study embryology. The breakthroughs in cloning were done on cancer grants to study gene regulation [35].

Yet, genetics soon assumed dominance over the field of cancer research just as it had with evolutionary biology (whose paradigms cancer biologists often propose for their own field). The founding document of the genetic (somatic mutation) theory of cancer appears to be that of Boveri [36]. Boveri was very much a cytologist and an embryologist, and he related the anomalies of cancer to those developmental anomalies caused by polyspermy and by chromosome elimination during nematode development, noting that such chromosomal rearrangements might be the cause of cancer. (Indeed, as Wunderlich [37] has shown, Boveri seems to be totally unaware of Morgan’s data for genes and did not use the term “mutation” at all. This was a later addition, probably by Morgan). The somatic mutation theory (SMT) still holds sway, claiming that cancer was due to mutations in the premalignant cell. Reviewing the embryological mechanisms of cancer, Cofre and Abdelhay [38] have recently written that “embryologists have expressed timidly” the idea that cancer can be seen as alterations of normal development and have met “with little success in leveraging the discussion that cancer could involve a set of conventional interactions used to build the embryo during morphogenesis.” However, I cannot view Barry Pierce’s [39] article “Carcinoma is to embryology as mutation is to genetics” as timid (it demands changes in the college curriculum), nor do Carlos Sonnenschein and Ana Soto, the founders of the Tissue Organizational Field Theory [40,41], hide the light of developmental cancer origins under a bushel. This failure to gain traction for a developmental approach to cancer is more likely due to the inability of the target to respond. But things may be changing. The basis for the allele-oriented SMT has recently been questioned [39–41], and the relevance of embryonic fields to cancer has been re-established [38–44]. Alterations in paracrine factor signaling in both the target and producer cells have been seen to initiate cancer formation, and embryonic processes such as epithelial-mesenchymal transformation are now seen as critical in metastasis. It is without question, though, that developmental biology helped establish oncology and has continued to help mold it. The rightful sovereign returns.

Having generated cell biology, immunology, genetics, neurobiology, and oncology, developmental biology still seems to be budding off new disciplines. Evolutionary developmental biology sees evolution as Huxley did, as changes in development (rather than changes in allele frequency) and focuses on the arrival of the fittest. Ecological developmental biology sees the environment as having instructive as well as permissive agency in normal development. Systems biology, which began with embryologically oriented philosophers such as Woodger and von Bertalanffy [45–47], attempts to fuse developmental biology, ecology, and physiology into an integrative science of becoming.

And other new disciplines are struggling to form an identity separate from their developmental parent discipline. Stem cell biology has its own meetings, its own journals, and its own professional societies, different from those of developmental biology. When Irving Weismann, one of the founders of the International Society for Stem Cell Research, became president of that organization, he threw down the gauntlet to developmental biology, saying [48],

“We are a field, a discipline, and an entire branch of science that brings new ideas, experiments, concepts, and medical translation. Like anything new, we are a threat to the established order, and at every kind of educational and research institution, to thrive, we must be recognized as entities, not as divisions of old entities.”

But it is not yet a truly independent field, as it has yet to propose anything different from developmental biology. All the articles in Stem Cell Reports are papers that would find a home in journals of developmental biology. At the moment, stem cell biology is a political, rather than an intellectual, bud from developmental biology, and it is performing important services in creating science-based educational accessibility and political guidelines, which the developmental biology societies have not done. Whether it becomes more than a medical aspect of developmental biology remains to be seen.

There are three main messages of this essay. The first is that developmental biology is not a confined, specified discipline—such as genetics, cell biology, immunology, oncology, neurobiology, and so forth. Developmental biology is not confined to any level of organization (in that genes, cells, tissues, organs, organisms, and ecosystems can each be studied developmentally). It can be studied in any species, organ system, or biome. Developmental biology remains pluripotent. The descendants of developmental biology—cell biology, genetics, immunology, neurobiology—are more differentiated and their potency much more restricted. They have boundaries. Surely, developmental biology has its own set of questions, perhaps the best questions of any science—How does the brain form? How do the bones of the arms become different from the bones of the legs, and why can’t we regenerate them like salamanders do? How do testes usually originate in people with a Y chromosome and ovaries in people with two X chromosomes? (And these are only a few of the questions in humans)—and it regenerates itself constantly as new techniques and hypotheses become available. Indeed, developmental biology has been called an “erotetic science,” differing from most other sciences in that it is driven by questions, not theories [49]. Thus, developmental biology is a stem cell discipline, one that regenerates itself while permitting some of its descendants to develop into their own fields.

The second message is that developmental biology remains a vital generative science. The induced pluripotential stem cells (iPSCs) are derived from the principles and discoveries of developmental biologists, as are the human beta-pancreatic cells now in clinical trials. The neural embryoids derived from such cells are now being used to study the mechanisms by which the Zika virus causes microcephaly. The 3D structure of chromatin and its remodeling during early mammalian development is becoming known, as are the mechanisms of X-chromosome inactivation. Developmental biology is also being expanded by identifying the interactions of the zygote-derived cells with those of symbiotic microbes to form organ gut, capillary, and immune cells. We are discovering how the turtle gets its shell and how the butterfly wing develops structural colors. We are in a new golden age of developmental biology.

The third message of this essay is that in the 21st century, many of the disciplines that had come from developmental biology are returning to a developmental framework, even if they don’t call it “developmental biology.” This is probably because developmental biology has always been a science about relationships in which context is critical [50], and the biology of the 21st century is focusing on relations, process, and context, rather than on entities. Thus, modern biology has come to the place where developmental biology has always been residing, a place of context-dependent interactions. Being relatively undifferentiated does not mean that developmental biology is immature [47,49–51]. Indeed, it is a science that was initiated with Aristotle and is now at the forefront of contemporary theories and methods. We can expect that even if developmental biology is not mentioned by name, the principles of developmental biology are becoming a framework integrating disciplines across biology.


I wish to thank Ron Amundson, Robert Auerbach, James Briscoe, Blanche Capel, David Epel, John Gearhart, Steve Klein, Alan Love, John Opitz, Larry Ruben, Sherrie Lyons, and Ken Zaret for their careful reading of this manuscript and for their insightful comments and criticisms.


  1. 1. Keller EF. Refiguring life: metaphors of twentieth century biology. New York: Columbia University Press; 1995.
  2. 2. Capel B. Presidential address. 76th Annual Meeting of the Society for Developmental Biology. 2017.
  3. 3. Gilbert SF. Expanding the temporal dimensions of developmental biology: The role of environmental agents in establishing adult-onset phenotypes. Biol. Theory 2011; 6: 65–72.
  4. 4. Wolpert L. Evolution of the cell theory. Philos. Trans. Roy. Soc. Lond. B. Biol. Sci. 1995; 349: 227–233.
  5. 5. Mylott A. The roots of cell theory in sap, spores, and Schleiden. Bloomington: Indiana University Press; 2011.
  6. 6. Duchesneau F. Genèse de la théorie cellulaire. Montreal: Librarie Philosophique Vrin.
  7. 7. Remak R. On the embryological basis of the cell theory Q. Rev. Micr. Sci 1862; 2: 277–284.
  8. 8. Chernyak L, Tauber A I. The birth of immunology: Metchnikoff, the embryologist. Cellular Immunol. 1988; 117: 218–233.
  9. 9. Gilbert SF. The embryological origins of the gene theory. J. Hist. Biol. 1978; 11: 307–351. pmid:11610436
  10. 10. Morgan TH, Sturtevant AH, Muller HJ, Bridges CB. The mechanism of Mendelian heredity. New York: Henry Holt; 1915.
  11. 11. Morgan TH. The theory of the gene. New Haven: Yale University Press; 1926
  12. 12. Gilbert SF. Bearing crosses: The historiography of genetics and embryology. Amer J Med Genet. 1998; 76: 168–182.
  13. 13. Morgan TH. The rise of genetics. Science. 1932; 76:261–288. pmid:17840456
  14. 14. Sapp J. Genesis; the evolution of biology. Oxford: Oxford University Press, 2003.
  15. 15. Beatty J. Genetics in the Atomic Age: The Atomic Bomb Casualty Commission. In: Benson KR, Maienschein J. Rainger R. editors. The expansion of American biology. New Brunswick: Rutgers University Press; 1991. Pp.284–324.
  16. 16. Friedman WE, Diggle PK. Charles Darwin and the origins of plant evolutionary developmental biology. Plant Cell. 2011; 23: 1194–1207. pmid:21515816
  17. 17. Chambers R. Vestiges of the natural history of creation. London: John Churchill; 1844.
  18. 18. Darwin C. The variation of animals and plants under domestication. New York: Appleton; 1896.
  19. 19. Winther RG. Darwin on variation and heredity. J Hist Biol 2000; 33: 425–455.
  20. 20. Gilbert SF, Opitz J, Raff RA. Resynthesizing evolutionary and developmental biology. Developmental Biology. 1996; 173: 357–372. pmid:8605997
  21. 21. Haeckel E. Generelle morphologie der organismen [General morphology of the organisms]. Berlin: G. Reimer; 1866.
  22. 22. Lyons S. Thomas Henry Huxley: the evolution of a scientist. Amherst, MA: Prometheus Press; 1999.
  23. 23. Gissis S. Spencer’s evolutionary entanglement: from liminal individuals to implicit collectivities. In Lidgard S, Nyhart LK, editors. Biological Individuality. Chicago: Chicago University Press; 2017. pp. 158–183.
  24. 24. Huxley TH. “Evolution in Biology,” in Darwiniana (1893). 2017 Dec 18.
  25. 25. Morgan TH. The Scientific Basis of Evolution. New York: W. W. Norton; 1932
  26. 26. Amundson R The changing role of the embryo in evolutionary thought: roots of evo-devo. Cambridge: Cambridge University Press; 2005.
  27. 27. Wolfe AJ. What does it mean to go public? the American response to Lysenkoism, reconsidered. Historical Stud. Nat. Sci. 2010; 40: 48–78.
  28. 28. Harrison RG. The outgrowth of the nerve fiber as a mode of protoplasmic movement. J Exp Zool. 1910; 9: 787846.
  29. 29. Ramón y Cajal S. Etudes sur la neurogenese de quelques vertebres. Moya: Madrid. 1929. English translation: Guth L. Studies in neurogenesis. Springfield, IL; Thomas; 1960.
  30. 30. Puelles L. Contributions to neuroembryology of Santiago Ramon y Cajal (1852–1934) and Joge F. Tello (1880–1958). Int. J. Devel. Biol. 2009; 53: 1145–1160.
  31. 31. Virchow RLK. Cellular pathology as based upon physiological and pathological histology. Chance F., translator. John Churchill: London; 1859. 2017 Dec 17.
  32. 32. Waddington CH. Cancer and the theory of organisers. Nature 1935; 135:606–608.
  33. 33. McKinnell RG. Cloning: A Biologist Reports. Minneapolis: U. Minnesota Press; 1985.
  34. 34. Edwards A. The impact of developmental biology on cancer research: an overview. Cancer Metastasis Rev 1999; 18: 175–180. pmid:10728982
  35. 35. Crowe N. Cancer, conflict, and the development of nuclear transplantation techniques. J. History of Biology 2014; 47: 63–205.
  36. 36. Boveri T. Zur Frage der Entstehung maligner Tumoren. Jena: Verlag von Gustav Fischer; 1914.
  37. 37. Wunderlich V. Early references to the mutational origin of cancer. Int. J. Epidemiol. 2007; 36: 246–247. pmid:17169945
  38. 38. Cofre J. Abdelhay E. Cancer is to embryology as mutation is to genetics: hypothesis of the cancer as embryological phenomenon. Sci. World J. 2017 ID 3578090.
  39. 39. Pierce GB. Carcinoma is to embryology as mutation is to genetics. Int. Comp. Biol. 1985; 25: 707–712.
  40. 40. Sonnenschein C, Soto A. A society of cells: cancer and control of cell proliferation. Oxford: Oxford University Press; 1999.
  41. 41. Sonnenschein C, Soto A. Carcinogenesis explained within the context of a theory of organisms. Progr. Biophys. Mol. Biol. 2016; 122: 70–76.
  42. 42. Weinberg RA. Coming full circle-from endless complexity to simplicity and back again. Cell 2014; 157: 267–271. pmid:24679541
  43. 43. Gilbert SF. and Epel D. Ecological developmental biology: the environmental regulation of development, health, and evolution. Sunderland, MA: Sinauer Associates; 2015
  44. 44. Aiello NC, Stanger BZ. 2016. Echoes of the embryo: using developmental biology toolkit to study cancer. Dis. Model Mech. 2016; 9: 105–114. pmid:26839398
  45. 45. Woodger JH. The concept of organism and the relation between embryology and genetics. Part II. Q. Rev. Biol. 1931; 5: 438–462.
  46. 46. von Bertalanffy L. Problems of life: an evaluation of modern biological thought. New York: Wiley; 1952.
  47. 47. Braukmann S. The organismic system theory of Ludwig von Bertalanffy (1926–1937). Biol. Zentralbl. 1996; 115: 197–205.
  48. 48. Weissman I. The ISSCR: who are we and where are we going? Cell Stem Cell. 2009; 5(2):151–153. pmid:19664988
  49. 49. Love AC. 2014. The erotetic organization of developmental biology. In: Minelli AA., and Pradeu T, editors. Towards a theory of development. Oxford: Oxford University Press; 2014 pp. 33–55.
  50. 50. Gilbert SF, Sarkar S. Embracing complexity: organicism for the twenty-first century. Developmental Dynamics 2000; 219: 1–9. pmid:10974666
  51. 51. Love AC. 2012. Formal and material theories in philosophy of science: a methodological interpretation. In de Regt HW, Okasha S, Hartmann S, editors. EPSA Philosophy of Science: Amsterdam 2009 (The European Philosophy of Science Association Proceedings, Vol. 1). Berlin: Springer; 2012; Pp. 175–185.

A vital class of membrane proteins are those involved in active or passive transport of materials across the cell membrane or other subcellular membranes surrounding organelles. For a cell or an organism to survive, it is crucial that the right substances enter cells (e.g. nutrients) and the right substances are transported out of them (e.g. toxins).

Passive and active transport

Molecules can cross biological membranes in several different ways depending on their concentration on either side of the membrane, their size and their charge. Some molecules, including water, can simply diffuse through the membrane without assistance. However, large molecules or charged molecules cannot cross membranes by simple diffusion. Charged molecules such as ions can move through channels passively, down electrochemical gradients. This movement is described as ‘downhill’, as the ions or molecules travel from an area of high concentration to an area of low concentration. This requires channel proteins but no energy input. Passive transport can also be mediated by carrier proteins that carry specific molecules such as amino acids down concentration gradients, again without any requirement for energy. Active transport moves species against concentration gradients and requires energy, which is obtained from ATP, from light, or from the downhill movement of a second type of molecule or ion within the same transporter (Figure 6).

Figure 6.Passive and active transport.

The different types of membrane proteins involved in passive and active transport are shown.

Passive transport

Passive transport is the movement of molecules across biological membranes down concentration gradients. This type of transport does not require energy. Channels form water-filled pores and thus create a hydrophilic path that enables ions to travel through the hydrophobic membrane. These channels allow downhill movement of ions, down an electrochemical gradient. Both the size and charge of the channel pore determine its selectivity. Different channels have pores of different diameters to allow the selection of ions on the basis of size. The amino acids that line the pore will be hydrophilic, and their charge will determine whether positive or negative ions travel through it. For example, Ca2+ is positively charged, so the amino acids lining the pores of Ca2+ channels are generally basic (i.e. they carry a negative charge).

Channels are not always open. They can be gated by ligands which bind to some part of the protein, either by a change in membrane potential (voltage gated) or by mechanical stress (mechanosensitive). The nicotinic acetylcholine receptor is an example of a ligand-gated ion channel which opens upon binding the neurotransmitter acetylcholine (Figure 7). The nicotinic acetylcholine receptor is a pentameric membrane protein composed of five subunits arranged in a ring, with a pore through the centre. In the closed state, the pore is blocked by large hydrophobic amino acid side chains which rotate out of the way upon acetylcholine binding to make way for smaller hydrophilic side chains, allowing the passage of ions through the pore. Opening of the nicotinic acetylcholine receptor allows rapid movement of Na+ ions into the cell and slower movement of K+ ions out of the cell, in both cases down the electrochemical gradient of the ion. The difference in gradients between Na+ and K+ across the membrane means that more Na+ enters the cell than K+ leaves it. This creates a net movement of positive charges into the cell, resulting in a change in membrane potential. Acetylcholine released by motor neurons at the neuromuscular junction travels across the synapse and binds to nicotinic acetylcholine receptors in the plasma membrane of the muscle cells, causing membrane depolarization. This depolarization of the muscle cells triggers Ca2+ release and muscle contraction.

Figure 7.The nicotinic acetylcholine receptor.

The pentameric structure of the receptor is shown, with the pore region (P) indicated. Transmembrane helices (M1–M4) are labelled in each subunit. The bilayer is shown in orange. Reproduced from Berridge, M.J. (2012) Cell Signalling Biology; doi:10.1042/csb0001003, with permission.

Carrier proteins are the other class of membrane proteins, apart from channels, which can facilitate passive transport of substances down concentration gradients. Carrier proteins transport molecules much more slowly than channels, as a number of conformational changes in the carrier are required for the transport of the solute across the membrane. A molecule such as a sugar binds to the carrier protein on one side of the membrane where it is present at a high concentration. Upon binding, the carrier changes conformation so that the sugar molecule then faces towards the opposite side of the membrane. The concentration of sugar on this side is lower, so dissociation occurs and the sugar is released. This is downhill movement and, although slower than movement through channels, it requires no energy.

The cystic fibrosis transmembrane conductance regulator (CFTR) is an ATP-dependent chloride ion (Cl) channel that has an important role in regulating the viscosity of mucus on the outside of epithelial cells. ATP is used to gate the channel, but the movement of Cl occurs down its electrochemical gradient, so does not require energy. A heritable change in the CFTR gene which results in a single amino acid deletion in the protein causes cystic fibrosis. This is a serious illness in which thick mucus accumulates in the lungs, causing a significantly lower than average life expectancy in patients who have the disease. Unimpaired ion transport is vital for our survival and health, and conditions such as cystic fibrosis highlight the need for research into these types of proteins.

Active transport

The transport of molecules across a membrane against a concentration gradient requires energy, and is referred to as active transport. This energy can be obtained from ATP hydrolysis (primary active transport), from light (as, for example, in the case of the bacterial proton pump bacteriorhodopsin), or from an electrochemical gradient of an ion such as Na+ or H+ (secondary active transport).

Calcium ions signal many events, including muscle contraction, neurotransmitter release and cellular motility. However, high cytoplasmic concentrations of Ca2+ are toxic to the cell. Therefore Ca2+ must be tightly regulated and removed from the cytoplasm either into internal stores (the ER, and the SR in muscle cells) or into the extracellular space. This Ca2+ removal is carried out by a family of Ca2+-ATPases, including the sarco/endoplasmic reticulum Ca2+-ATPase (SERCA), which hydrolyse ATP to move Ca2+ against its electrochemical gradient into the ER and SR (Figure 8). There are Ca2+-ATPases in the ER, Golgi and plasma membrane, and despite their sequence similarity, these proteins are differentially targeted to the appropriate membrane. These Ca2+ pumps are primary active transporters. SERCA moves two Ca2+ ions into the ER or SR for every ATP molecule that is hydrolysed. The pump undergoes a cycle of binding ATP and phosphorylation, and undergoes large conformational changes every time it transports a pair of Ca2+ ions. SERCA is a P-type ATPase (so called because it is phosphorylated during ion transport). There are many P-type ATPases, and they are conserved in evolution across many species. The Na+/K+-ATPase is one of these P-type ATPases, and it works in a similar way to SERCA to pump Na+ out of the cell and K+ into the cell using energy derived from the hydrolysis of ATP. We have now obtained three-dimensional structures of SERCA in a number of conformational states, which allow scientists to visualize the transport process.

Figure 8.The sarco/endoplasmic reticulum Ca2+-ATPase (SERCA).

The crystal structure of SERCA in the ADP- and Ca2+-bound state is shown. D351 (in red) is the residue phosphorylated during the movement of Ca2+ ions into the ER or SR. The three cytoplasmic domains, phosphorylation (P), nucleotide binding (N) and actuator (A) are labelled. ADP is shown in yellow and Ca2+ ions in green. Protein Data Bank (PDB) code 2ZBD, rendered using PDB Protein Workshop.

Secondary active transport requires an ion electrochemical gradient to drive the uphill transport of another solute. The downhill movement of one species drives the uphill movement of the other. This can be symport (in which both types of molecule or ion travel across the membrane in the same direction) or antiport (in which the two species travel in opposite directions), as shown in Figure 9.

Figure 9.Symport and antiport.

The two types of co-transport are shown, with examples.

In order to transport glucose into cells, the Na+–glucose symporter uses the electrochemical gradient of Na+ across the plasma membrane. The concentration of Na+ is much higher outside the cell, and the inside of the cell is negatively charged relative to the outside, so by allowing Na+ to travel down its electrochemical gradient, these transporters can move glucose uphill, into the cell and against its concentration gradient. This is referred to as symport, as both Na+ and glucose travel in the same direction—in this case into the cell. In order for this symport to be sustainable, the Na+ gradient must be maintained. This is done by the Na+/K+-ATPase, which uses ATP to pump the Na+ back into the extracellular space, thus maintaining a low intracellular Na+ concentration.

Both Na+ and Ca2+ are present at much higher concentrations outside the cell than inside it. Like the Na+–glucose symporter, the Na+–Ca2+ exchanger uses the electrochemical gradient of Na+ across the plasma membrane to move a second species (Ca2+) against its electrochemical gradient. However, in this case the transporter is an antiporter, as it uses the concentration gradient of one substance moving in (Na+) to move another (Ca2+) out of the cell. This antiporter has an exchange rate of three Na+ ions in to two Ca2+ ions out. It moves Ca2+ out of the cell faster than the plasma membrane equivalents of SERCA, but has a lower affinity for Ca2+ than these P-type ATPases. Again this transporter relies on the Na+/K+-ATPase to maintain the low intracellular Na+ concentration.

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