Cellular Biology 1: The Cell

While some scientists were arguing over the theory of spontaneous generation, other scientists were making discoveries leading to a better understanding of what we now call the cell theory. The classic cell theory has three basic tenets:

1. All living things are composed of one or more cells.
2. The cell is the basic unit of structure and function of all living things.
3. All cells arise from other living cells (the principle of biogenesis).

As scientists have continued to study the cell and expand our understanding of cell biology, the modern cell theory has three additional tenets:

1. Hereditary information (DNA) is passed from cell to cell during cell division.
2. All cells within similar species have mostly the same structural and chemical composition.
3. Energy flow occurs within the cell.

Today, these tenets are fundamental to our understanding of life on earth. However, the modern cell theory grew out of the collective work of many scientists.

The Origins of Cell Theory

Despite Hooke’s early description of cells, their significance as the fundamental unit of life was not yet recognised. Nearly 200 years later, in 1838, Matthias Schleiden (1804–1881), a German botanist who made extensive microscopic observations of plant tissues, described them as being composed of cells. Visualising plant cells was relatively easy because plant cells are clearly separated by their thick cell walls. Schleiden believed that cells formed through crystallisation, rather than cell division.

Theodor Schwann (1810–1882), a noted German physiologist, made similar microscopic observations of animal tissue. In 1839, after a conversation with Schleiden, Schwann realised that similarities existed between plant and animal tissues. This laid the foundation for the idea that cells are the fundamental components of plants and animals.

In the 1850s, two Polish scientists living in Germany pushed this idea further, culminating in what we recognise today as the cell theory. In 1852, Robert Remak (1815–1865), a prominent neurologist and embryologist, published convincing evidence that cells are derived from other cells as a result of cell division. However, this idea was questioned by many in the scientific community. Three years later, Rudolf Virchow (1821–1902), a well-respected pathologist, published an editorial essay entitled “Cellular Pathology,” which popularised the concept of cell theory using the Latin phrase omnis cellula a cellula (“all cells arise from cells”), which is essentially the third tenet of modern cell theory. Given the similarity of Virchow’s work to Remak’s, there is some controversy as to which scientist should receive credit for articulating cell theory.

Cell Characteristics

DNA and RNA

DNA (deoxyribonucleic acid) is the hereditary material in human cells and nearly all other organisms, serving as the blueprint for life and the foundation of genetics. In eukaryotes, it normally consists of two long strands that form a double helix, with each strand composed of nucleotides. These nucleotides include a phosphate group, a sugar molecule (deoxyribose), and one of four nitrogenous bases: adenine (A), thymine (T), cytosine (C), or guanine (G). The specific sequence of these bases encodes genetic information, which determines an organism's genotype—the complete set of genes inherited from its parents. This genetic information guides the synthesis of proteins, which in turn influence an organism's phenotype, or the observable traits and characteristics. The double helix structure of DNA allows for accurate replication during cell division, ensuring genetic continuity across generations and maintaining the stability of the genotype. The relationship between genotype and phenotype is central to the study of genetics, as it explains how variations in DNA sequences can lead to differences in physical traits, behaviours, and susceptibility to diseases.

RNA (ribonucleic acid), in contrast, is typically single-stranded and plays a crucial role in translating the genetic code from DNA into proteins, which are key determinants of an organism's phenotype. Like DNA, RNA is composed of nucleotides, but with a few key differences: the sugar in RNA is ribose instead of deoxyribose, and RNA contains uracil (U) instead of thymine. RNA is central to the expression of the genotype into a phenotype through several types of RNA molecules, each with specific functions. Messenger RNA (mRNA) carries the genetic instructions from DNA to the ribosomes, where proteins are synthesised based on the sequence encoded by the genotype. Transfer RNA (tRNA) assists in assembling amino acids into proteins, ensuring that the correct sequence is followed to produce functional proteins that influence the organism's traits. Ribosomal RNA (rRNA) forms the core of ribosomes, the cellular structures where protein synthesis occurs. This flow of genetic information from DNA to RNA to protein is known as the central dogma of molecular biology and is fundamental to the process by which an organism's genotype is expressed as a phenotype, shaping the organism's physical appearance, behaviour, and overall biology.

Cell Structures

Eukaryotic organisms include protozoans, algae, fungi, plants, and animals. Some eukaryotic cells are independent, single-celled microorganisms, whereas others are part of multicellular organisms. The cells of eukaryotic organisms have several distinguishing characteristics. Above all, eukaryotic cells are defined by the presence of a nucleus surrounded by a complex nuclear membrane. Also, eukaryotic cells are characterised by the presence of membrane bound organelles in the cytoplasm. Organelles such as mitochondria, the endoplasmic reticulum (ER), Golgi apparatus, lysosomes, and peroxisomes are held in place by the cytoskeleton, an internal network that supports transport of intracellular components and helps maintain cell shape (Figure 1.7). The genome of eukaryotic cells is packaged in multiple, rod-shaped chromosomes as opposed to single circular prokaryotic chromosomes.

Eukaryotic cells display a wide variety of different cell morphologies and shapes. Possible shapes include spheroid, ovoid, cuboidal, cylindrical, flat, lenticular, fusiform, discoidal, crescent, ring stellate, and polygonal (Figure 1.8). Some eukaryotic cells are irregular in shape, and some are capable of changing shape. The shape of a particular type of eukaryotic cell may be influenced by factors such as its primary function, the organisation of its cytoskeleton, the viscosity of its cytoplasm, the rigidity of its cell membrane or cell wall if present, and the physical pressure exerted on it by the surrounding environment and/or adjoining cells. Yeast cells can change morphology, and this can increase infectiveness and virulence.

The prokaryotic cell has a relatively simple construction. They consist of a cytoplasm, a gel-like substance composed of water and dissolved chemicals needed for growth, which is contained within a plasma membrane (also called a cell membrane or cytoplasmic membrane) and a cell wall. Chromosomal DNA, which contains the genetic blueprints of the cell, is concentrated in a nucleoid, and ribosomes are used to produce proteins. Some prokaryotic cells may also possess additional structures such as flagella (whip-like structures protruding from the cell used for locomotion), pili (hair-like appendages used for attachment and transfer of genetic material), fimbriae (hair-like structures allowing adhesion) and capsules (gelatinous layer around the outside of a cell to provide protection) (Figure 1.9). Some prokaryotic species can produce internal structures for survival called endospores when conditions are adverse for the cell. These structures contain all the necessary components to allow the endospore to germinate once it encounters an environment where it can survive and grow. The structures inside a cell are analogous to the organs inside a human body, with unique structures suited to specific functions.

In most prokaryotic cells, morphology is maintained by the cell wall in combination with cytoskeletal elements. Individual cells of a particular prokaryotic organism (species) are typically similar in shape (have a similar cell morphology). Although many thousands of prokaryotic organisms have been identified, only a few different cell morphologies are commonly seen microscopically and include round (cocci), rod (bacillus) and spiral (spirillum) shapes (Figure 1.10). In addition to cellular shape, prokaryotic cells of the same species may group together in certain common and distinctive arrangements depending on the plane of cell division (Figure 1.11) and this aids in presumptive identifications.

Archaeal (belonging to archaea) membranes are fundamentally different from bacterial and eukaryotic membranes in a few significant ways. First, archaeal membrane phospholipids are formed with ether linkages (chemical bond connecting oxygen molecule to alkyl or aryl organic groups), in contrast to the ester linkages found in bacterial or eukaryotic cell membranes. Second, archaeal phospholipids have branched chains, whereas those of bacterial and eukaryotic cells are straight chained. Finally, although some archaeal membranes can be formed of bilayers like those found in bacteria and eukaryotes, other archaeal plasma membranes are lipid monolayers.

Proteins on the cell’s surface are important for a variety of functions, including cell-to-cell communication, and sensing environmental conditions and pathogenic virulence factors. Membrane proteins and phospholipids may have carbohydrates (sugars) associated with them forming glycoproteins or glycolipids, respectively. These glycoprotein and glycolipid complexes extend out from the surface of the cell, allowing the cell to interact with the external environment (Figure 1.12). Glycoproteins and glycolipids in the plasma membrane can vary considerably in chemical composition among archaea, bacteria, and eukaryotes, allowing scientists to use them to characterise unique species.

Plasma membranes from different cell types have unique phospholipids that contain specific fatty acids. The analysis of these fatty acids, known as phospholipid-derived fatty acid (PLFA) profiles, can be used to identify and differentiate cell types. Archaea, bacteria, and eukaryotes each have distinct PLFA profiles, which provide a reliable method for distinguishing between these domains of life and can offer insights into the environmental conditions and metabolic activities of different organisms.

Some prokaryotic cells, namely cyanobacteria (type of bacteria that produce oxygen) and photosynthetic bacteria, have membrane structures that enable them to perform photosynthesis. Photosynthesis is the process by which green plants, algae, and some bacteria convert sunlight, carbon dioxide, and water into glucose (sugar) and oxygen, using the energy from light to power the synthesis of organic compounds. These structures consist of an infolding of the plasma membrane that encloses photosynthetic pigments such as green chlorophylls and bacteriochlorophylls. In cyanobacteria, these membrane structures are called thylakoids; in photosynthetic bacteria, they are called chromatophores, lamellae or chlorosomes.

Cell Wall

Structures that enclose the cytoplasm and internal structures of the cell are known collectively as the cell envelope. Cells of fungi, algae, plants, and even some protists have cell walls. Depending upon the type of eukaryotic cell, cell walls can be made of a wide range of materials, including:

• Cellulose, a complex carbohydrate, used by fungi and plants
• Biogenic silica (a form of silica), also known as opal
• Calcium carbonate, chemical compound found in rocks, shells, and marine organism skeletons
• Agar, a gelatinous substance derived from algae
• Carrageenan, a polysaccharide (large sugar molecule)
• Chitin, flexible polysaccharide used by fungi (and also the exoskeleton of arthropods)

In general, all cell walls provide structural stability for the cell and protection from environmental stresses such as desiccation, changes in osmotic pressure, and traumatic injury.

In prokaryotic cells, the structures of the cell envelope vary depending on the type of cell and organism. Most (but not all) prokaryotic cells have a cell wall, but the makeup of this cell wall varies. The major component of bacterial cell walls, and unique only to bacteria, is called peptidoglycan (or murein). Structurally, peptidoglycan resembles a layer of meshwork or fabric (Figure 1.13), with each layer composed of long chains of alternating molecules of N-acetylglucosamine (NAG) and N-acetylmuramic acid (NAM). The structure of the long chains has significant two-dimensional tensile strength due to the formation of peptide bridges that connect NAG and NAM within each peptidoglycan layer. In gram-negative bacteria, tetrapeptide chains extending from each NAM unit are directly cross-linked, whereas in gram-positive bacteria, these tetrapeptide chains are linked by pentaglycine cross-bridges. Peptidoglycan subunits are made inside of the bacterial cell and then exported and assembled in layers, giving the cell its shape.

Since peptidoglycan is unique to bacteria, many antibiotic drugs are designed to interfere with peptidoglycan synthesis, weakening the cell wall and making bacterial cells more susceptible to the effects of osmotic pressure. In addition, certain cells of the human immune system are able to recognise bacterial pathogens by detecting peptidoglycan on the surface of a bacterial cell. These cells then engulf and destroy the bacterial cell, using enzymes such as lysozyme, which breaks down and digests the peptidoglycan in their cell walls.

 

Gram-positive and gram-negative are bacterial classifications based on the Gram staining protocol (used in staining microscopic specimens), used to differentiate the two common types of cell wall structures (Figure 1.14). Gram-positive cells have a cell wall consisting of many layers of peptidoglycan totalling 30–100 nm in thickness. These peptidoglycan layers are commonly embedded with teichoic acids (TAs), carbohydrate chains that extend through and beyond the peptidoglycan layer. TA is thought to stabilise peptidoglycan by increasing its rigidity. It also plays a role in the ability of pathogenic gram-positive bacteria such as Streptococcus species to bind to certain proteins on the surface of host cells, enhancing their ability to cause infection. In addition to peptidoglycan and TAs, some bacteria such as the Mycobacteriaceaefamily, have an external layer of waxy mycolic acids (long chains of fatty acids) in their cell wall which affects stain infiltration. These bacteria are referred to as acid-fast, since acid-fast stains must be used to penetrate the mycolic acid layer for purposes of microscopy (Figure 1.15).

 

Gram-negative cells have a much thinner layer of peptidoglycan, no more than about 4 nm thick, and the overall structure of their cell envelope is more complex. In gram-negative cells, a gel-like matrix occupies the periplasmic space between the cell wall and the plasma membrane, and there is a second lipid bilayer called the outer membrane, which is external to the peptidoglycan layer (Figure1.14). This outer membrane is attached to the peptidoglycan by murein lipoprotein. The outer leaflet of the outer membrane contains the molecule lipopolysaccharide (LPS), which functions as an endotoxin (toxic components released into environment upon bacterial cell death) in infectionsinvolving gram-negative bacteria, contributing to symptoms such as fever, haemorrhaging and septic shock. Each LPS molecule is composed of Lipid A, a core polysaccharide, and an O side chain that is composed of sugar-like molecules that comprise the external face of the LPS (Figure 1.16). The composition of the O side chain varies between different species and strains of bacteria. Parts of the O side chain called antigens can be detected using serological or immunological tests to identify specific pathogenic strains like Escherichia coli O157:H7, a deadly strain of bacteria that causes bloody diarrhea and kidney failure. 

Archaeal cell wall structure differs from that of bacteria in several significant ways. First, archaeal cell walls do not contain peptidoglycan; instead, they contain a similar polymer called pseudopeptidoglycan (pseudomurein) in which NAM is replaced with a different subunit, or other glycoproteins or polysaccharides that serve as the cell wall instead of pseudopeptidoglycan.

There are also several archaea species that appear to lack cell walls entirely.  Although almost all prokaryotic cells have cell walls, some may have additional cell envelope structures exterior to the cell wall, such as glycocalyces and S-layers. A glycocalyx is a sugar coat, of which there are two important types: capsules and slime layers.

Capsules and Slime Layers

A bacterial capsule is a polysaccharide layer that completely envelopes the cell (Figure 1.17). It is well organised and tightly packed, which explains its resistance to staining under the microscope. The capsule offers protection from a variety of different threats to the cell, such as desiccation, hydrophobic toxic materials (i.e. detergents) and bacterial viruses. The capsule can enhance the ability of bacterial pathogens to cause disease and can provide protection from phagocytosis (engulfment by white blood cells known as phagocytes). Lastly, it can help in attachment to surfaces. The ability to produce a capsule can contribute to a microbe’s pathogenicity (ability to cause disease) because the capsule can make it more difficult for phagocytic cells (such as white blood cells) to engulf and kill the microorganism. Streptococcus pneumoniae, for example, produces a capsule that is well known to aid in this bacterium’s pathogenicity. Capsules are difficult to stain for microscopy and so negative staining techniques are typically used.

 

A bacterial slime layer is similar to the capsule in that it is typically composed of polysaccharides and it completely surrounds the cell (Figure 1.18). It also offers protection from various threats, such as desiccation and antibiotics. It can also allow for adherence to surfaces. So, how does it differ from the capsule? A slime layer is a loose, unorganised layer that is easily stripped from the cell that made it, as opposed to a capsule which integrates firmly around the bacterial cell wall.

 

Glycocalyces such as the capsule or slime layer allow bacteria to adhere to surfaces, aiding in the formation of biofilms (colonies of microbes that form in layers on surfaces). In nature, most microbes live in mixed communities within biofilms, partly because the biofilm affords them some level of protection. Biofilms generally hold water like a sponge, preventing desiccation. They also protect cells from predation and hinder the action of antibiotics and disinfectants. These properties are advantageous to the microbes living in a biofilm, but they present challenges in a clinical setting, where the goal is often to eliminate microbes. the formation of a biofilm can occur quickly and aids in the colonisation, maturation and then dispersion of certain bacterial populations such as Pseudomonas aeruginosa.

Some bacteria have a highly organised layer made of secreted proteins or glycoproteins that self-assemble into a matrix on the outer part of the cell wall. This regularly structured S-layer is anchored into the cell wall, although it is not considered to be officially part of the cell wall in bacteria. S-layers have very important roles for the bacteria that have them, particularly in the areas of growth and survival, and cell integrity.

S-layers help maintain overall rigidity of the cell wall and surface layers, as well as cell shape, which are important for reproduction. S-layers protect the cell from ion/pH changes, osmotic stress, detrimental enzymes, bacterial viruses, and predator bacteria. They can provide cell adhesion to other cells or surfaces. For pathogenic bacteria they can provide protection from phagocytosis.

Cytosol

The cytoplasm is a thick, usually colourless solution that fills each cell and is enclosed by the cell membrane. Cytoplasm presses against the cell membrane, filling out the cell and giving it its shape. Sometimes cytoplasm acts like a watery solution and sometimes it takes on a more gel-like consistency. In eukaryotic cells, the cytoplasm includes all of the material inside the cell but outside the nucleus, which contains its own watery substance called nucleoplasm. All of the organelles in eukaryotic cells, such as the endoplasmic reticulum and mitochondria, are located in the cytoplasm. The cytoplasm helps to keep them in place. It is also the site of most metabolic activities in the cell, and it allows materials to pass easily throughout the cell.

The portion of the cytoplasm surrounding organelles is called cytosol, which is the liquid part of the cytoplasm. It is composed of about 80 percent water and also contains dissolved salts, fatty acids, sugars, amino acids, and proteins such as enzymes. These dissolved substances are needed to keep the cell alive and carry out metabolic processes. For example, enzymes dissolved in cytosol break down larger molecules into smaller products that can then be used by organelles of the cell. Waste products are also dissolved in the cytosol before they are taken in by vacuoles or expelled from the cell.

Though prokaryotic cells do not have organelles (they do have ribosomes), they still have cytoplasm. It is within the cytoplasm that most cellular activities occur, including the many metabolic pathways that occur within organelles, such as photosynthesis and aerobic respiration.

Organelles

Although most eukaryotic cells have only one nucleus (Figure 3.3), exceptions exist. For example, protozoans of the genus Paramecium typically have two complete nuclei: a small nucleus that is used for reproduction (micronucleus) and a large nucleus that directs cellular metabolism (macronucleus). Additionally, some fungi transiently form cells with two nuclei, called heterokaryotic cells, during sexual reproduction. Cells whose nuclei divide, but whose cytoplasm does not, are called coenocytes.

Nuclear Envelope

The nucleus is bound by a complex nuclear membrane, often called the nuclear envelope, that consists of two distinct lipid bilayers that are contiguous with each other (Figure 1.19). Despite these connections between the inner and outer membranes, each membrane contains unique lipids and proteins on its inner and outer surfaces. The nuclear envelope contains nuclear pores, which are large, rosette-shaped protein complexes that control the movement of materials into and out of the nucleus. The overall shape of the nucleus is determined by the nuclear lamina, a meshwork of intermediate filaments found just inside the nuclear envelope membranes. Outside the nucleus, additional intermediate filaments form a looser mesh and serve to anchor the nucleus in position within the cell.

Nucleolus

The nucleolus is a dense region within the nucleus where ribosomal RNA (rRNA) biosynthesis occurs. In addition, the nucleolus is also the site where assembly of ribosomes begins. Pre-ribosomal complexes are assembled from rRNA and proteins in the nucleolus; they are then transported out to the cytoplasm, where ribosome assembly is completed (Figure 1.20).

 

All cellular life has a DNA genome organised into one or more chromosomes. Prokaryotic chromosomes are typically circular, haploid (unpaired) and not bound by a complex nuclear membrane. Prokaryotic DNA and DNA-associated proteins are concentrated within the nucleoid region of the cell (Figure 1.21). In general, prokaryotic DNA interacts with nucleoid-associated proteins (NAPs) that assist in the organisation and packaging of the chromosome. In bacteria, NAPs function like histones, which are the DNA-organising proteins found in eukaryotic cells. In archaea, the nucleoid is organised by either NAPs or histone-like DNA organising proteins.

 

Mitochondria

The large, complex organelles in which aerobic cellular respiration occurs in eukaryotic cells are called mitochondria (Figure 1.22). The term “mitochondrion” was first coined by German microbiologist Carl Benda in 1898 and was later connected with the process of respiration by Otto Warburg in 1913. Scientists during the 1960s discovered that mitochondria have their own genome and 70S ribosomes. The mitochondrial genome was found to be bacterial when it was sequenced in 1976. These findings ultimately supported the endosymbiotic theory proposed by Lynn Margulis, which states that mitochondria originally arose through an endosymbiotic event in which a bacterium capable of aerobic cellular respiration was taken up by phagocytosis into a host cell and remained as a viable intracellular component.

Each mitochondrion has two lipid membranes. The outer membrane is a remnant of the original host cell’s membrane structures. The inner membrane was derived from the bacterial plasma membrane. The electron transport chain for aerobic respiration uses integral proteins embedded in the inner membrane. The mitochondrial matrix, corresponding to the location of the original bacterium’s cytoplasm, is the current location of many metabolic enzymes. It also contains mitochondrial DNA and 70S ribosomes. Invaginations of the inner membrane, called cristae, evolved to increase surface area for the location of biochemical reactions. The folding patterns of the cristae differ among various types of eukaryotic cells and are used to distinguish different eukaryotic organisms from each other.

 

Scientists often call mitochondria (singular = mitochondrion) “powerhouses” or “energy factories” of both plant and animal cells because they are responsible for making adenosine triphosphate (ATP), the cell’s main energy-carrying molecule. ATP represents the cell's short-term stored energy. Cellular respiration is the process of making ATP using the chemical energy in glucose and other nutrients. In mitochondria, this process uses oxygen and produces carbon dioxide as a waste product. In fact, the carbon dioxide exhaled with every breath comes from the cellular reactions and metabolic functions that produce carbon dioxide as a by-product (waste).

Ribosomes

All cellular life synthesises proteins, and organisms in the bacteria, archaea and eukaryotic domains (Figure 1.6) of life possess ribosomes, structures responsible for protein synthesis. However, ribosomes in each of the three domains are structurally different. Ribosomes, themselves, are constructed from proteins, along with ribosomal RNA (rRNA). Prokaryotic ribosomes are found in the cytoplasm and are called 70S ribosomes because they have a size of 70S with two subunits (Figure 1.23), whereas eukaryotic cytoplasmic ribosomes have a size of 80S, also with two subunits. In terms of size and composition, this makes them distinct from the ribosomes of prokaryotic cells. The S stands for Svedberg unit, a measure of sedimentation in an ultracentrifuge, which is based on size, shape, and surface qualities of the structure being analysed. Although they are the same size, bacterial and archaeal ribosomes have different proteins and rRNA molecules, and the archaeal versions are more like their eukaryotic counterparts than to those found in bacteria.

The two types of eukaryotic ribosomes are defined by their location in the cell: free ribosomes and membrane-bound ribosomes. Free ribosomes are found in the cytoplasm and serve to synthesise water-soluble proteins; membrane-bound ribosomes are found attached to the rough endoplasmic reticulum and make proteins for insertion into the cell membrane or proteins destined for export from the cell. 

The differences between eukaryotic and prokaryotic ribosomes are clinically relevant because certain antibiotic drugs are designed to target one or the other. For example, cycloheximide targets eukaryotic action, whereas chloramphenicol targets prokaryotic ribosomes. Since human cells are eukaryotic, they generally are not harmed by antibiotics that destroy the prokaryotic ribosomes in bacteria. However, sometimes negative side effects may occur because mitochondria in human cells contain prokaryotic ribosomes.  

 

Endomembrane System

The endomembrane system, unique to eukaryotic cells, is a series of membranous tubules, sacs, and flattened disks that synthesise many cell components and move materials around within the cell (Figure 1.24). Because of their larger cell size, eukaryotic cells require this system to transport materials that cannot be dispersed by diffusion alone. The endomembrane system comprises several organelles and connections between them, including the endoplasmic reticulum, Golgi apparatus, lysosomes, and vesicles.

 

The endoplasmic reticulum (ER) is an interconnected array of tubules and cisternae (flattened sacs) with a single lipid bilayer (Figure 1.25). The spaces inside of the cisternae are called lumen of the ER. There are two types of ER, rough endoplasmic reticulum (RER) and smooth endoplasmic reticulum (SER). These two different types of ER are sites for the synthesis of distinctly different types of molecules. RER is studded with ribosomes bound on the cytoplasmic side of the membrane. These ribosomes make proteins destined for the plasma membrane (Figure 1.25). Following synthesis, these proteins are inserted into the membrane of the RER. Small sacs of the RER containing these newly synthesised proteins then bud off as transport vesicles and move either to the Golgi apparatus for further processing, directly to the plasma membrane, to the membrane of another organelle, or out of the cell. Transport vesicles are single-lipid, bilayer, membranous spheres with hollow interiors that carry molecules. SER does not have ribosomes and, therefore, appears “smooth.” It is involved in biosynthesis of lipids, carbohydrate metabolism, and detoxification of toxic compounds within the cell.

 

Golgi apparatus

The Golgi apparatus was discovered within the endomembrane system in 1898 by Italian scientist Camillo Golgi (1843–1926), who developed a novel staining technique that showed stacked membrane structures within the cells of Plasmodium, the causative agent of malaria. The Golgi apparatus is composed of a series of membranous disks called dictyosomes, each having a single lipid bilayer, that are stacked together (Figure 1.26).

Enzymes in the Golgi apparatus modify lipids and proteins transported from the ER to the Golgi, often adding carbohydrate components to them, producing glycolipids, glycoproteins, or proteoglycans. Glycolipids and glycoproteins are often inserted into the plasma membrane and are important for signal recognition by other cells or infectious particles. Different types of cells can be distinguished from one another by the structure and arrangement of the glycolipids and glycoproteins contained in their plasma membranes. These glycolipids and glycoproteins commonly also serve as cell surface receptors. Cell surface receptors allow the cell to detect and respond to external signals by binding to specific molecules, such as hormones, neurotransmitters, or growth factors. Upon binding, the receptor triggers a series of intracellular events, leading to a specific cellular response, such as changes in gene expression, enzyme activity, or ion channel function.

Transport vesicles leaving the ER fuse with a Golgi apparatus on its receiving, or cis, face. The proteins are processed within the Golgi apparatus, and then additional transport vesicles containing the modified proteins and lipids pinch off from the Golgi apparatus on its outgoing, or trans, face. These outgoing vesicles move to and fuse with the plasma membrane or the membrane of other organelles.

 

Enzymes

Enzymes, which are produced by living cells and may be present in numerous cellular organelles, are catalysts in biochemical reactions (like digestion) and are usually proteins. Each enzyme is specific for the substrate (a reactant that binds to an enzyme) upon which it acts. Enzymes can function to break molecular bonds, to rearrange bonds, or to form new bonds. Some of these critical biochemical reactions include building larger molecules from smaller components (such as what occurs during DNA replication or synthesis of microtubules) and breaking down larger molecules into smaller components (such as when harvesting chemical energy from nutrient molecules). An example of an enzyme is salivary amylase, which breaks down amylose, a component of starch.

In animal cells, the lysosomes are the cell’s “garbage disposal.” Digestive enzymes within the lysosomes aid the breakdown of proteins, polysaccharides, lipids, nucleic acids, and even worn-out organelles. In single-celled eukaryotes, lysosomes are important for digestion of the food they ingest and the recycling of organelles. These enzymes are active at a much lower pH (more acidic) than those located in the cytoplasm. Many reactions that take place in the cytoplasm could not occur at a low pH, thus the advantage of compartmentalising the eukaryotic cell into organelles is apparent.

Lysosomes also use their hydrolytic enzymes to destroy disease-causing organisms that might enter the cell. A good example of this occurs in a group of white blood cells called macrophages, which are part of your body’s immune system. In a process known as phagocytosis, a section of the plasma membrane of the macrophage invaginates (folds in) and engulfs a pathogen. The invaginated section, with the pathogen inside, then pinches itself off from the plasma membrane and becomes a vesicle. The vesicle fuses with a lysosome. The lysosome’s hydrolytic enzymes then destroy the pathogen (Figure 1.27).

 

Chloroplast

Plant cells and algal cells contain chloroplasts, the organelles in which photosynthesis occurs (Figure 1.28). All chloroplasts have at least three membrane systems: the outer membrane, the inner membrane, and the thylakoid membrane system. Inside the outer and inner membranes is the chloroplast stroma, a gel-like fluid that makes up much of a chloroplast’s volume, and in which the thylakoid system floats. The thylakoid system is a highly dynamic collection of folded membrane sacs. It is where the green photosynthetic pigment chlorophyll is found and the light reactions of photosynthesis occur. In most plant chloroplasts, the thylakoids are arranged in stacks called grana (singular: granum), whereas in some algal chloroplasts, the thylakoids are free floating.

 

Other organelles similar to mitochondria have arisen in other types of eukaryotes, but their roles differ. Hydrogenosomes are found in some anaerobic eukaryotes and serve as the location of anaerobic hydrogen production. Hydrogenosomes typically lack their own DNA and ribosomes. Kinetoplasts are a variation of the mitochondria found in some eukaryotic pathogens. In these organisms, each cell has a single, long, branched mitochondrion in which kinetoplast DNA, organised as multiple circular pieces of DNA, is found concentrated at one pole of the cell.

Cytoskeleton

Both prokaryotic cells and eukaryotic cells have an internal cytoskeleton. The bacterial cytoskeleton helps sense the environment and ensure communication between cells. These communications are aided by conjugation tubes and nanotubes and even by membrane vesicles and can also confer increased virulence when certain groups of bacteria form a biofilm or are located in the same vicinity.

Much more is known about the cytoskeleton of eukaryotic cells and these are made of microfilaments, intermediate filaments, and microtubules. This matrix of fibres and tubes provides structural support as well as a network over which materials can be transported within the cell and on which organelles can be anchored (Figure 1.29). For example, the process of exocytosis involves the movement of a vesicle via the cytoskeletal network to the plasma membrane, where it can release its contents.

 

Microfilaments

Microfilaments are composed of two intertwined strands of actin, each composed of actin monomers forming filamentous cables 6 nm in diameter (Figure 1.30). The actin filaments work together with motor proteins, like myosin, to effect muscle contraction in animals or the amoeboid movement of some eukaryotic microbes. In ameboid organisms, actin can be found in two forms: a stiffer, polymerised, gel form and a more fluid, unpolymerised soluble form. Actin in the gel form creates stability in the ectoplasm, the gel-like area of cytoplasm just inside the plasma membrane of ameboid protozoans.

Adenosine triphosphate (ATP) powers actin to assemble its filamentous form, which serves as a track for the movement of a motor protein we call myosin. This enables actin to engage in cellular events requiring motion, such as cell division in eukaryotic cells and cytoplasmic streaming, which is the cell cytoplasm's circular movement in plant cells. Actin and myosin are plentiful in muscle cells. When your actin and myosin filaments slide past each other, your muscles contract.

Temporary extensions of the cytoplasmic membrane called pseudopodia (meaning “false feet”) are produced through the forward flow of soluble actin filaments into the pseudopodia, followed by the gel-sol cycling of the actin filaments, resulting in cell motility. Once the cytoplasm extends outward, forming a pseudopodium, the remaining cytoplasm flows up to join the leading edge, thereby creating forward locomotion. Beyond amoeboid movement, microfilaments are also involved in a variety of other processes in eukaryotic cells, including cytoplasmic streaming (the movement or circulation of cytoplasm within the cell), cleavage furrow formation during cell division, and muscle movement in animals (Figure 1.30). These functions are the result of the dynamic nature of microfilaments, which can polymerise and depolymerise relatively easily in response to cellular signals, and their interactions with molecular motors in different types of eukaryotic cells.

 

Intermediate Filaments

Intermediate filaments (Figure 1.31) are a diverse group of cytoskeletal filaments that act as cables within the cell. They are termed “intermediate” because their 10-nm diameter is thicker than that of actin but thinner than that of microtubules. They are composed of several strands of polymerised subunits that, in turn, are made up of a wide variety of monomers. Intermediate filaments tend to be more permanent in the cell and maintain the position of the nucleus. They also form the nuclear lamina (lining or layer) just inside the nuclear envelope. Additionally, intermediate filaments play a role in anchoring cells together in animal tissues. The intermediate filament protein desmin is found in desmosomes, the protein structures that join muscle cells together and help them resist external physical forces. The intermediate filament protein keratin is a structural protein found in hair, skin, and nails.

 

Microtubules

Microtubules (Figure 1.32) are a third type of cytoskeletal fibre composed of tubulin dimers (α tubulin and β tubulin). These form hollow tubes 23 nm in diameter that are used as girders within the cytoskeleton. Like microfilaments, microtubules are dynamic and have the ability to rapidly assemble and disassemble. Microtubules also work with motor proteins (such as dynein and kinesin) to move organelles and vesicles around within the cytoplasm. Additionally, microtubules are the main components of eukaryotic flagella and cilia, composing both the filament and the basal body components.

 

In addition, microtubules are involved in cell division, forming the mitotic spindle that serves to separate chromosomes during mitosis and meiosis. The mitotic spindle is produced by two centrosomes, which are essentially microtubule-organising centres, at opposite ends of the cell. Each centrosome is composed of a pair of centrioles positioned at right angles to each other, and each centriole is an array of nine parallel microtubules arranged in triplets (Figure 1.33).

 

Centrioles

Centrioles are cylindrical, microtubule-based structures found in most eukaryotic cells, playing a critical role in cell division and the organisation of microtubules within the cytoplasm. Each centriole is composed of nine triplet microtubules arranged in a cylindrical shape, resembling a hollow tube, and these microtubules are made up of tubulin proteins, which form the structural backbone of the centriole. Typically, centrioles exist in pairs, arranged perpendicularly to each other within a region of the cell called the centrosome. This pair of centrioles is often referred to as the diplosome.

During cell division, centrioles are essential for organising the mitotic spindle, a structure made of microtubules that segregates chromosomes into daughter cells, ensuring accurate chromosome separation. Before a cell enters mitosis, the centrioles replicate, ensuring that each daughter cell inherits a pair of centrioles. This duplication process, which occurs during the S phase of the cell cycle, is tightly regulated to ensure proper cell division. In addition to their role in cell division, centrioles also serve as basal bodies for the formation of cilia and flagella, which are hair-like structures involved in cell movement or the movement of fluids across the cell surface. As basal bodies, centrioles act as templates for the assembly of the microtubules that make up the core of cilia and flagella.

Beyond their involvement in cell division and the formation of cilia and flagella, centrioles contribute to the organisation of the microtubule network within the cell, which is crucial for maintaining cell shape, enabling intracellular transport, and positioning organelles. The process of centriole duplication, part of the centrosome cycle, is tightly synchronised with the cell cycle, with duplication beginning in the S phase and continuing through the G2 phase to ensure that two centrosomes are present by the time the cell enters mitosis. Proteins such as Polo-like kinase 4 (Plk4) regulate this duplication process, and abnormalities in centriole duplication can lead to issues like aneuploidy (an incorrect number of chromosomes), often associated with cancer.

Centrioles are also clinically significant, as disorders related to defective cilia and flagella, such as primary ciliary dyskinesia and polycystic kidney disease, can be traced back to problems with centriole function. Additionally, abnormalities in centriole duplication can lead to centrosome amplification, resulting in abnormal cell division and contributing to tumorigenesis. Mutations affecting proteins involved in centriole function or duplication can lead to developmental disorders, as proper cell division is crucial for embryonic development. Centrioles are conserved across a wide range of eukaryotic species, highlighting their fundamental role in cellular processes. However, not all eukaryotic cells possess centrioles; for instance, higher plants and certain fungi lack centrioles and have alternative mechanisms for organising their microtubules. Overall, centrioles are essential organelles that ensure the proper organisation of microtubules during cell division, contribute to the formation of cilia and flagella, and play a critical role in maintaining cellular structure and function. Their precise regulation is vital for normal cell division and function, and disruptions in their structure or duplication can lead to various diseases, including cancer and ciliopathies.

Fimbriae and Pili

Fimbriae and pili are structurally similar and because differentiation between the two is problematic, these terms are often used interchangeably. The term fimbriae commonly refers to short bristle-like proteins projecting from the cell surface by the hundreds. Fimbriae enable a cell to attach to surfaces and to other cells. For pathogenic bacteria, adherence to host cells is important for colonisation, infectivity, and virulence. Adherence to surfaces is also important in biofilm formation.

The term pili (singular: pilus) commonly refers to longer, less numerous protein appendages that aid in attachment to surfaces (Figure 1.34). A specific type of pilus, called the F pilus or sex pilus, is important in the transfer of DNA between bacterial cells, which occurs between members of the same generation when two cells physically transfer or exchange parts of their respective genomes, including antimicrobial resistance genes.

 

Bacterial movement typically involves the use of flagella, although there are a few other possibilities as well (such as the use of type IV pili for twitching motility), however the most common type of bacterial movement is swimming, which is accomplished with the use of a flagellum (singular) or flagella (plural).

Flagella are structures used by cells to move in aqueous environments. Bacterial flagella act like propellers. They are stiff spiral filaments composed of flagellin protein subunits that extend outward from the cell and spin in solution. The basal body is the motor for the flagellum and is embedded in the plasma membrane (Figure 1.35). A hook region connects the basal body to the filament. Gram-positive and gram-negative bacteria have different basal body configurations due to the differences in cell wall structure.

 

Different types of motile bacteria exhibit different arrangements of flagella (Figure 1.36). A bacterium with a singular flagellum, typically located at one end of the cell (polar), is said to have a monotrichous flagellum. An example of a monotrichously flagellated bacterial pathogen is Vibrio cholerae, the gram-negative bacterium that causes cholera. Cells with amphitrichous flagella have a flagellum or tufts of flagella at each end. An example is Spirillum minor, the cause of spirillary (Asian) rat-bite fever (also known as sodoku). Cells with lophotrichous flagella have a tuft at one end of the cell. The gram-negative bacillus Pseudomonas aeruginosa, an opportunistic pathogen known for causing many infections, including “swimmer’s ear” and burn wound infections, has lophotrichous flagella. Flagella that cover the entire surface of a bacterial cell are called peritrichous flagella. The gram-negative bacterium Escherichia coli shows a peritrichous arrangement of flagella.  

Directional movement depends on the configuration of the flagella. Bacteria can move in response to a variety of environmental signals, including light (phototaxis), magnetic fields (magnetotaxis) using magnetosomes, and, most commonly, chemical gradients (chemotaxis). Purposeful movement toward a chemical attractant, like a food source, or away from a repellent, like a poisonous chemical, is achieved by increasing the length of runs and decreasing the length of tumbles. When running, flagella rotate in a counter clockwise (CCW) direction, allowing the bacterial cell to move forward. In a peritrichous bacterium, the flagella are all bundled together in a very streamlined way (Figure 1.37), allowing for efficient movement. When tumbling, flagella are splayed out while rotating in a clockwise direction, creating a looping motion, and preventing meaningful forward movement but reorienting the cell toward the direction of the attractant. When an attractant exists, runs and tumbles still occur; however, the length of runs is longer, while the length of the tumbles is reduced, allowing overall movement toward the higher concentration of the attractant. When no chemical gradient exists, the lengths of runs and tumbles are more equal, and overall movement is more random (Figure 1.38).

The stimuli that ‘inform’ these movements are detected by protein receptors embedded within their membrane, called chemoreceptors, which bind specific molecules. Binding typically results in methylation or phosphorylation of the chemoreceptor itself, which triggers an elaborate protein pathway that eventually impacts the rotation of the flagellar motor. The bacteria engage in temporal sensing, where they compare the concentration of a substance with the concentration obtained just a few seconds (or microseconds) earlier. In this way they gather information about the orientation of the concentration gradient of the substance.

 

 

Some eukaryotic cells use flagella for locomotion; however, eukaryotic flagella are structurally distinct from those found in prokaryotic cells. Whereas the prokaryotic flagellum is a stiff, rotating structure, a eukaryotic flagellum is more like a flexible whip composed of nine parallel pairs of microtubules surrounding a central pair of microtubules. This arrangement is referred to as a 9+2 array. The parallel microtubules use dynein motor proteins to move relative to each other, causing the flagellum to bend.

Cilia

Cilia (singular: cilium) are a similar external structure found in some eukaryotic cells. Unique to eukaryotes, cilia are shorter than flagella and often cover the entire surface of a cell; however, they are structurally similar to flagella (a 9+2 array of microtubules) and use the same mechanism for movement. A structure called a basal body is found at the base of each cilium and flagellum. The basal body, which attaches the cilium or flagellum to the cell, is composed of an array of triplet microtubules similar to that of a centriole but embedded in the plasma membrane. Because of their shorter length, cilia use a rapid, flexible, waving motion. In addition to motility, cilia may have other functions such as sweeping particles past or into cells. For example, ciliated protozoans use the sweeping of cilia to move food particles into their mouthparts, and ciliated cells in the mammalian respiratory tract beat in synchrony to sweep mucus and debris up and out of the lungs (Figure 1.39).

 

Cell Junctions

Epithelial tissues cover the outside of organs and structures in the body and line the lumens of organs in a single layer or multiple layers of cells. Epithelial cells fit together tightly to support their protective role in the body. This is accomplished as cells are attached to a basement membrane and each cell is connected to the adjacent cells by special attachments (junctions) which can also aid in cell communication (Figure 1.40).

 

Extracellular matrix

Cells of animals and some protozoans do not have cell walls to help maintain shape and provide structural stability. Instead, these types of eukaryotic cells produce an extracellular matrix (ECM) for this purpose. They secrete a sticky mass of carbohydrates and proteins into the spaces between adjacent cells (Figure 1.41). Some protein components assemble into a basement membrane to which the remaining extracellular matrix components adhere. Proteoglycans typically form the bulky mass of the extracellular matrix while fibrous proteins, like collagen, provide strength. Both proteoglycans and collagen are attached to fibronectin proteins, which, in turn, are attached to integrin proteins. These integrin proteins interact with transmembrane proteins in the plasma membranes of eukaryotic cells that lack cell walls.

In animal cells, the extracellular matrix allows cells within tissues to withstand external stresses and transmits signals from the outside of the cell to the inside. The amount of extracellular matrix is quite extensive in several types of connective tissues, and variations in the extracellular matrix can give several types of tissues their distinct properties. In addition, a host cell’s extracellular matrix is often the site where microbial pathogens attach themselves to establish infection. For example, Streptococcus pyogenes, the bacterium that causes strep throat and various other infections, binds to fibronectin in the extracellular matrix of the cells lining the oropharynx (upper region of the throat).