The cell

Summary

The cell is the basic structural and functional unit of living organisms. While unicellular organisms (e.g., bacteria, protozoa) consist of a single cell capable of sustaining life, multicellular organisms (e.g., animals, land plants) consist of numerous highly specialized and diverse cells organized into various types of tissue. Cells are surrounded by a membrane composed of a lipid bilayer with embedded proteins. Depending on their cell structure, organisms are classified prokaryotes or eukaryotes. Prokaryotes, which encompass the domains of the Bacteria and the Archaea, are unicellular organisms that lack membrane-bound organelles such as a nucleus and mitochondria (see bacteria overview). Eukaryotes are unicellular and multicellular organisms, whose cell or cells contain various specialized, membrane-bound organelles such as a nucleus and mitochondria.

Cell types

Cell types are classified as either prokaryotic or eukaryotic. Prokaryotes are unicellular organisms that encompass the domains of Bacteria and Archaea. They consist of a single cytoplasm-filled compartment enclosed by a cell membrane. Eukaryotes contain a nucleus and other membrane-bound cell organelles. Eukaryotes encompass all multicellular organisms as well as some unicellular ones (protozoa). Eukaryotic cells are larger (100–10,000-fold) than prokaryotic cells and possess a significantly higher degree of complexity in terms of structure.

Eukaryotes Prokaryotes
Nucleus
  • Present
  • Absent

Location of DNA
  • Nucleus
  • Cytoplasm
DNA storage form
Amount of noncoding DNA
  • 70–98% (lower gene density)
  • 5–25% (higher gene density)

External boundaries
Compartmentalization
  • Membranes separate cellular compartments within the cytosol
  • No compartmentalization
Locomotive structures (flagellum)
  • Consist of bundles of microtubules and the motor protein dynein that are surrounded by a plasma membrane
  • Consist of repeating subunits of the protein flagellin (filament), a hook, and a motor complex that is anchored in the cell membrane

Prokaryotic cells do not have a nucleus!

Cell membrane

Both prokaryotes and eukaryotes have cell membranes. The cell membrane provides a boundary to the cell interior and is an essential component of living systems. Eukaryotic cells also have intracellular membranes that envelop individual organelles and enable specialized processes to occur within in separation from cytoplasmic processes. Most prokaryotic and plant cells furthermore possess a cell wall, which envelops the cell membrane and protects cells from external influences.

Cell membrane structure

The cell membrane is composed of a lipid bilayer with embedded or attached membrane proteins. The synthesis of membrane components occurs in the smooth endoplasmic reticulum (sER).

Lipid bilayer

  • Structure: The fundamental building blocks are amphiphilic lipids such as phospholipids or sphingolipids, which possess a polar head (e.g., phosphate, sphingosine) and hydrophobic tails (fatty acids).
    • Distribution of nonpolar and polar groups: In an aqueous solution, the nonpolar hydrocarbon tails face inward, while the polar heads form a boundary to water in both directions. As a result, stable lipid bilayers develop, forming a spherical entity (e.g., cells or vesicles).
    • Distribution of membrane lipids: The different types of lipids are distributed asymmetrically between the two leaflets of the membrane.
      • Outer lipid layer: rich in phosphatidylcholine and sphingomyelin
      • Inner lipid layer: rich in phosphatidylserine, phosphatidylethanolamine, and phosphatidylinositol
  • Characteristics
    • Permeability
      • Almost impermeable to polar molecules
      • Highly permeable to nonpolar molecules and water
    • Fluidity: The fluidity of the membrane lipid bilayer changes depending on the composition of the lipid bilayer and temperature of the environment.
    • Diffusion: The fluidity of the lipid bilayer allows for movement of individual molecules within the membrane.

Membrane proteins

Examples of asymmetrically distributed membrane components
Integral membrane proteins Transmembrane proteins
  • Na+/K+-ATPase
Integral monotopic proteins
  • Certain cyclooxygenases
Peripheral membrane proteins Extracellularly directed
Intracellularly directed
  • Phospholipase C

Because of their fluidity, membranes are also permeable to water and some small molecules like O2, even without the use of specific channels or transporters. This characteristic is termed semi-permeable!

Glycocalyx

Membrane functions

  • Protects the cell from the external environment
  • Transport of substances from the inside to the outside of the cell or from the outside to the inside of the cell
  • Signal transduction: conversion of extracellular signals into intracellular reactions
  • Cell identification
    • Every cell expresses specific proteins on its surface that are mostly glycosylated (glycoproteins).
    • These glycoproteins are highly specific for each cell type and allow for the distinction of self cells from one another as well as from foreign cells.
  • Electrical excitability
    • Generation of an electrochemical gradient across the membrane creates a membrane potential.
    • Excitation activates voltage-gated ion channels, temporarily decreasing the negative membrane potential (depolarization).
  • Cell junctions: : formed by anchor proteins (cell adhesion molecules), which are anchored to the cytoskeleton and protrude outside of the cell

Cell organelles

Cellular organelles are compartments within cells that are enveloped by a membrane and have a highly specific function. Eukaryotes contain numerous organelles, whereas prokaryotes lack compartmentalization.

Overview of the most important cell organelles
Cellular organelles Structure Function
Nucleus
  • Double membrane
Endoplasmic reticulum (ER)
  • Branched membrane system
  • Synthesis of proteins, membrane components, etc.
Golgi apparatus
  • Enveloped, disc-shaped vesicle system
  • Modification and packaging of products for export out of the cell
Mitochondria
  • Double membrane
  • Intramembranous space
  • Matrix
  • Energy production
  • Various metabolic pathways
Lysosomes
  • Small enveloped vesicles
  • Loaded with hydrolytic enzymes
  • Degradation of foreign and self molecules
Peroxisomes
  • Small enveloped vesicles
  • Loaded with various enzymes such as catalases

Cell nucleus

Structure

The nucleus is the control center of the cell. It is surrounded by a double membrane and contains all of the cell's genetic material except mitochondrial DNA.

Nuclear envelope

The nuclear membrane consists of an inner and outer membrane, each composed of a lipid bilayer.

Nuclear content

Functions

Endoplasmic reticulum

The endoplasmic reticulum (ER) is an extensive network of membranes that is directly connected to the outer nuclear membrane. The ER forms a channel system of elongated cavities. The most important function is the synthesis of cellular components and cell export products. The ER can be microscopically and functionally differentiated into the rough and smooth ER.

Structure

Functions

Golgi apparatus

The Golgi apparatus receives vesicles, especially from the ER and is responsible for further distribution of the substances (proteins and lipids) to their specific target structure like the lysosomes or the cell membrane.

Structure

Functions

Defective labeling of lysosomal acid hydrolases in the Golgi apparatus leads to I-cell disease.

Two steps forward (COPII - anterograde transport) and one step back (COPI - retrograde transport)

Mitochondria

Mitochondria are often described as the “powerhouses” of the cell due to their central role in the synthesis of ATP, a vital source of energy for the body. They are composed of a double membrane, the intramembranous space, and the matrix. Various mitochondrial types can be differentiated according to the inner membrane structure.

Structure

The structure and DNA of mitochondria resemble those of prokaryotes. Mitochondria are believed to originally have been prokaryotes that evolved into endosymbionts living inside eukaryotes (see symbiogenesis).

Mitochondrial membrane

There are two, highly specialized mitochondrial membranes that surround the mitochondrion. They provide the framework for the electron transport chain and ATP production.

Outer membrane

  • Structure: smooth
  • Permeability: interspersed with pores, highly permeable for various molecules

Inner membrane

  • Structure: convoluted
  • Permeability: impermeable, especially to ions; however the inner membrane contains many different highly specific transport proteins
  • Characteristic component: cardiolipin (stabilizes the enzymes of oxidative phosphorylation)

Carriers of the inner mitochondrial membrane

Specific transporters regulate the transport of substances through the inner membrane.

In the malate-aspartate shuttle, only the electrons of NADH and not NADH itself are transported across the inner mitochondrial membrane!

Mitochondrial matrix

Function

Symbiogenesis

The DNA and ribosomes of mitochondria resemble those of prokaryotes. The discovery of this produced the endosymbiotic theory of mitochondrial evolution, which states that mitochondria were originally independent prokaryotic bacteria with the special ability to produce energy through oxidative phosphorylation that were eventually engulfed by eukaryotic cells. As a result, the prokaryotic cells lost parts of their DNA and their ability to live independently, while the eukaryotic host cell became dependent on the energy produced by the incorporated bacterium.

Lysosomes

Lysosomes can be regarded as the cell's waste disposal system. Their main function is intracellular digestion, e.g., the degradation of polymers into monomers.

Structure

  • Small spherical organelles that are surrounded by a lipid bilayer and filled with digestive hydrolytic enzymes responsible for the degradation of macromolecules.
    • Hydrolytic enzymes: lipases, glucosidases, acidic phosphatases, nucleases, endoproteases (e.g., cathepsins )
    • Acidic environment (pH value of ∼ 5)
      • Optimal pH value for hydrolytic enzymes
      • Maintained by the active transport of H+ through the membrane H+-ATPase

The main enzyme of lysosomes is acidic phosphatase!

Function

Lysosomes play an important role in adaptive immunity. Antigen presenting cells (e.g., macrophages, dendritic cells) internalize antigens and degrade them by proteolysis within lysosomes. Afterwards, the resulting peptides are loaded onto MHC class II molecules, delivered to the cell surface and presented to naive T cells.

References:[1]

Peroxisomes

Peroxisomes are spherical organelles surrounded by a single membrane. They contain enzymes that oxidize amino acids and fatty acids utilizing oxygen.

Structure

  • Relatively small, round, membrane-enclosed vesicles

Function

In Zellweger syndrome, peroxisome formation and function is impaired, leading to the accumulation of cytotoxic hydrogen peroxide.

Refsum disease is an autosomal recessive disorder of insufficient α-oxidation of branched-chain fatty acids: phytanic acid cannot be metabolized to pristanic acid leading to adolescent onset of progressive ataxia, sensorineural hearing loss, scaling skin, cataracts, and night blindness.

Adrenoleukodystrophy is an X-linked recessive disorder of β-oxidation as a result from a mutation in the ABCD1 gene: very long chain fatty acids (VLCFA) build up in the adrenal glands, white matter of the brain, and testicles leading to adrenal insufficiency, cognitive impairment, and progressive vision, hearing, and motor deterioration.

Cytosol and ribosomes

Cytosol

The cytosol, also termed matrix, is enclosed by the cell membrane. In prokaryotes, almost all metabolic pathways occur directly in the cytosol, whereas in eukaryotes, several of these processes occur in cell organelles that are separated from the cytosol by a membrane (compartmentalization).

Structure

  • Water, dissolved ions, and small molecules (70%)
  • Proteins, e.g., enzymes involved in metabolic pathways (30%)

Function

The cytoplasm surrounds the nucleus and consists of the cytosol and the cell organelles.

Ribosomes

Ribosomes are very large molecule complexes of RNA and proteins, which are located in the cytosol, on the cytosolic side of the rER and within the mitochondria. The ribosome is the site of protein synthesis (translation).

Structure

Localization

Function

Cytosolic proteins (such as tubulin) are synthesized on free ribosomes. Lysosomal and membrane proteins are synthesized on ribosomes of the rER!

Cytoskeleton

The cytoskeleton is a network of filaments extending throughout the cytosol.

Overview

  • Functions
    • Stability and movement of the cell and its organelles
    • Transport processes within the cell
    • Essential for cell division
  • Structure: composed of filaments and accessory proteins
    • Filaments: elongated cell structures composed of monomers
      • RBCs contain a special kind of cytoskeleton filament on the cytosolic side of their cell membrane that consists of the filamentous protein spectrin. If forms a meshwork with other proteins like band 3, ankyrin, and band 4.1 proteins.
    • Accessory proteins: responsible for various functions of the cytoskeleton (motion, attachment and detachment of monomers, etc.)

The most important cytoskeletal elements

Filament Structure Accessory protein Function

Actin filaments (Microfilaments)

  • Diameter ∼7 nm
  • Monomer
    • G-Actin
    • Polymerize to F-Actin filaments through ATP consumption
  • Double helix of two polymer actin strands forms the actual filament
Intermediate filaments (IFs)
  • Intermediate filaments do not interact with motor proteins
  • Plectin: cross-links and stabilizes intermediate filaments
  • Cell stability

Microtubules

  • Diameter ∼ 25 nm
  • Composed of 13 concentrically arranged tubulin molecules
  • Polymerization: GTP-containing tubulin dimers (each composed of an α- and a β-tubulin) are deposited at the (+) end. 2 GTP are bound to each of the tubulin dimers.
  • Depolymerization: GTP spontaneously hydrolyzes to GDP in one of the β-tubulins, with destabilization of the microtubule
  • Microtubules can form various filament types:

The spectrin-based cytoskeleton of RBCs is deficient in hereditary spherocytosis.

Intermediate filaments can be used as immunohistochemical tumor markers to detect the origin of a neoplasm.

Drugs that disrupt microtubules: Microtubules Get Constructed Very Poorly: Mebendazole, Griseofulvin, Colchicine, Vincristine/Vinblastine, Paclitaxel!

Negative end Near Nucleus, while Positive end Points to the Periphery - The negative end of the microtubule is oriented towards the nucleus and the positive end is oriented towards the periphery of the cell.

Kin (keen) to go out (anterograde), Dying to come back home (retrograde). Kinesin transports anterograde (from – → +) along the microtubule. Dynein transports retrograde (from – → +) along the microtubule.

Cell junctions

The cells of the body are connected to other cells and the surrounding structures by cell-cell junctions and cell-matrix junctions. The type and number of junctions varies between different cell types. While red blood cells do not form cell junctions, epithelial cells are tightly connected to one another and with the basal lamina.

Occluding junctions

Anchoring junctions (adhering junctions)

Anchoring junctions are mechanical attachments between cells. Several forms can be differentiated depending on function.

Communicating junctions

Communicating junctions permit the passage of electrical or chemical signals.

Auto-antibodies directed against components of the cell junctions are formed in autoimmune blistering diseases, e.g., in pemphigus vulgaris (antidesmosome antibodies), in bullous pemphigoid (antihemidesmosome antibodies).

Clinical significance

  • 1. Goljan EF. Rapid Review Pathology. Philadelphia, PA: Elsevier Saunders; 2018.
last updated 06/17/2019
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