Cell Structure & Organelles

Cell biology forms the foundation of all biomedical science. Every living organism is composed of cells — the smallest unit capable of carrying out the processes of life. Understanding cell architecture is essential for comprehending how tissues function in health and how they fail in disease.

Prokaryotes vs Eukaryotes

Cells fall into two fundamental categories. Prokaryotic cells, found in bacteria and archaea, lack a membrane-bound nucleus. Their DNA is a single circular chromosome located in a region called the nucleoid, and they have no membrane-enclosed organelles. Prokaryotes reproduce by binary fission and are typically 1–10 µm in diameter.

Eukaryotic cells — found in animals, plants, fungi, and protists — are considerably more complex. They possess a true nucleus bounded by a double nuclear envelope perforated by nuclear pore complexes (NPCs). NPCs are ~120 nm gated channels that regulate bidirectional transport of proteins and RNA between nucleus and cytoplasm. The nucleus contains the cell's DNA organised into linear chromosomes associated with histone proteins to form chromatin. The nucleolus, a non-membrane-bound organelle within the nucleus, is the site of ribosomal RNA (rRNA) transcription and ribosome subunit assembly.

The Endomembrane System

The endoplasmic reticulum (ER) is a vast network of membranous tubules and cisternae continuous with the outer nuclear membrane. Rough ER is studded with ribosomes on its cytoplasmic face and is the primary site of synthesis and co-translational translocation of secretory, membrane, and lysosomal proteins. Protein folding and N-linked glycosylation begin in the rough ER lumen, assisted by molecular chaperones (BiP/GRP78, calnexin, calreticulin). Misfolded proteins are retained and targeted for ER-associated degradation (ERAD) via the ubiquitin-proteasome pathway. Smooth ER lacks ribosomes and is involved in lipid and steroid hormone synthesis, detoxification of drugs and toxins (cytochrome P450 enzymes in hepatocytes), and calcium storage (particularly in muscle, where it is called the sarcoplasmic reticulum).

The Golgi apparatus consists of a stack of flattened membranous cisternae organised with defined cis (receiving) and trans (shipping) faces. Vesicles arriving from the ER deliver cargo to the cis-Golgi; as proteins transit through medial to trans cisternae, they undergo further glycan processing, phosphorylation, and sulfation. The trans-Golgi network (TGN) sorts proteins into vesicles destined for the plasma membrane, lysosomes, or secretory granules. COPII vesicles mediate ER→Golgi transport; COPI vesicles handle retrograde (Golgi→ER) transport and intra-Golgi trafficking; clathrin-coated vesicles bud from the TGN for lysosomal targeting.

Energy-Producing Organelles

Mitochondria are double-membrane organelles responsible for aerobic ATP production. The outer membrane is permeable to small molecules via porins; the inner membrane is highly impermeable and is extensively folded into cristae, maximising the surface area available for the electron transport chain (ETC) and ATP synthase. The mitochondrial matrix contains enzymes for the TCA cycle, fatty acid β-oxidation, and amino acid catabolism. Critically, mitochondria contain their own circular DNA (~16.6 kb in humans), encode 13 inner membrane proteins, and have their own ribosomes — evidence of endosymbiotic origin from an ancestral α-proteobacterium. Mitochondria are inherited maternally and mutations in mitochondrial DNA cause a spectrum of diseases (MELAS, Leber's hereditary optic neuropathy).

Degradative Organelles

Lysosomes are membrane-bound vesicles containing over 60 acid hydrolases (proteases, lipases, nucleases, glycosidases) active at pH 4.5–5.0, maintained by V-type H⁺-ATPase proton pumps. They degrade cargo delivered by endocytosis, phagocytosis, and autophagy. Genetic defects in lysosomal enzymes cause lysosomal storage diseases — Gaucher disease (glucocerebrosidase deficiency), Tay-Sachs (β-hexosaminidase A deficiency), Niemann-Pick (sphingomyelinase deficiency). Peroxisomes are small organelles that carry out oxidative reactions including fatty acid β-oxidation (long-chain) and detoxification of hydrogen peroxide by catalase. Defective peroxisome biogenesis causes Zellweger syndrome.

The Cytoskeleton

The cytoskeleton is a dynamic network of protein polymers providing structural integrity, driving cell motility, and organising intracellular transport. Actin microfilaments (F-actin, 7 nm diameter) are assembled from G-actin monomers and generate force for cell migration, phagocytosis, and cytokinesis. The branched actin network at the leading edge (lamellipodium) is nucleated by the Arp2/3 complex. Intermediate filaments (8–10 nm) are tissue-specific: keratins in epithelial cells, vimentin in mesenchymal cells, desmin in muscle, neurofilaments in neurons, and lamins lining the inner nuclear envelope. They provide mechanical strength and are less dynamic than actin or microtubules. Microtubules (25 nm) are polar polymers of α/β-tubulin that form the mitotic spindle during cell division and serve as tracks for motor proteins: kinesin (anterograde, toward the plus end, i.e., toward the cell periphery) and dynein (retrograde, toward the minus end/centrosome). Cilia and flagella are specialised microtubule-based structures with a 9+2 axonemal arrangement.

Vesicular Trafficking and Endocytosis

Vesicular trafficking moves proteins between compartments. Endocytosis internalises extracellular material: receptor-mediated endocytosis (clathrin-coated pits) selectively internalises ligand-receptor complexes (e.g., LDL via LDLR in familial hypercholesterolaemia); macropinocytosis internalises large fluid volumes; phagocytosis (macrophages, neutrophils) engulfs large particles including bacteria. Exocytosis releases vesicle contents by membrane fusion — constitutive (e.g., collagen secretion) or regulated (e.g., insulin release from β cells, neurotransmitter release).

Clinical Correlations

Defects in cell structure underlie many diseases. Duchenne muscular dystrophy results from dystrophin mutations disrupting the link between actin and the extracellular matrix. Primary ciliary dyskinesia (Kartagener syndrome) causes immotile cilia due to dynein arm defects. Colchicine and vinca alkaloids disrupt microtubule polymerisation, halting mitosis in cancer cells. Taxanes (paclitaxel) stabilise microtubules, preventing depolymerisation and also arresting mitosis.