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Cell Structure and Differentiation

1. The Cell: An Overview

Every cell in the human body is the smallest living structural and functional unit. Animal cells are eukaryotic — they possess a distinct, membrane-enclosed nucleus surrounded by cytoplasm that contains a system of membranous organelles, non-membranous macromolecular assemblies, and polymerized cytoskeletal proteins. The average adult human body contains approximately 40 trillion cells of hundreds of histologically distinct types.

The cell contains highly organized physical structures called intracellular organelles that are critical for function. Without mitochondria alone, more than 95% of the cell's energy release from nutrients would cease immediately.

— Guyton and Hall Textbook of Medical Physiology; Junqueira's Basic Histology, 17e

2. The Cell Membrane (Plasma Membrane)

The cell membrane envelops the cell and is a thin, pliable, elastic structure only 7.5–10 nanometers thick. Its approximate composition:

55% proteins
25% phospholipids
13% cholesterol
4% other lipids
3% carbohydrates

Lipid Bilayer

The basic structure is a lipid bilayer — a double-layered film of lipids, each layer one molecule thick, continuous over the entire cell surface. Three main types of membrane lipids:

Lipid	Role
Phospholipids	Most abundant; hydrophilic phosphate head faces outward, hydrophobic fatty acid tails face inward
Sphingolipids	Protection from harmful factors, signal transmission, adhesion
Cholesterol	Controls fluidity and permeability of the bilayer

Membrane Proteins

Large globular proteins are interspersed in the lipid film. Integral proteins penetrate all the way through the membrane, forming channels and transporters. Peripheral proteins are attached to the surface. Many are enzymes or receptors.

Eukaryotic cell intracellular architecture — nucleus, microtubules, actin, ribosomes, transport vesicles

3. Membranous Organelles

All major organelles are covered by lipid–protein membranes. These include: cell membrane, nuclear membrane, endoplasmic reticulum (ER), mitochondria, lysosomes, peroxisomes, and Golgi apparatus.

Endoplasmic Reticulum (ER)

The ER is a network of tubules and cisternae occupying a large part of the cytoplasm.

Rough (Granular) ER: Studded with ribosomes on its outer surface. Ribosomes (composed of RNA and proteins) synthesize new protein molecules. The rough ER is directly continuous with the nuclear membrane, allowing efficient information exchange.
Smooth (Agranular) ER: Lacks attached ribosomes. Functions in synthesis of lipid substances, detoxification of drugs/poisons, and other intrareticular enzyme processes.

Golgi Apparatus

The Golgi apparatus consists of 4 or more stacked layers of thin, flat, enclosed vesicles near the nucleus. Small ER vesicles pinch off from the ER and fuse with the Golgi, which:

Processes, packages, and routes proteins for export outside the cell
Forms lysosomes and secretory vesicles

Lysosomes

Vesicular organelles (250–750 nm diameter) that bud off from the Golgi. Filled with up to 40 different hydrolase (digestive) enzymes. They digest:

Damaged cellular structures
Ingested food particles
Unwanted matter (bacteria, viruses)

Lysosomes are especially numerous in disease-fighting white blood cells and macrophages.

Mitochondria

The powerhouses of the cell. Mitochondria generate ATP via oxidative phosphorylation — coupling respiration to ATP generation. They contain their own DNA and ribosomes and replicate independently of the cell nucleus.

Peroxisomes

Contain oxidative enzymes including catalase. Oxidize fatty acids and detoxify hydrogen peroxide, protecting the cell from oxidative damage.

4. The Nucleus

The nucleus is the cell's control center, housing the genome. It contains:

Chromatin: DNA wound around histone proteins (nucleosomes). Condensed chromatin (heterochromatin) is transcriptionally silent; open chromatin (euchromatin) is active.
Nucleolus: Site of ribosomal RNA synthesis and ribosome assembly.
Nuclear envelope: Double membrane perforated by nuclear pores that regulate transport of RNA and proteins.

Each mature human cell produces a maximum of ~8,000–10,000 proteins rather than the potential 20,000–25,000 possible if all genes were expressed.

5. The Cytoskeleton

The cytoskeleton provides structural support and enables cell movement. Three main components:

Component	Diameter	Functions
Microtubules	~25 nm	Cell shape, intracellular transport, mitotic spindle
Microfilaments (Actin)	~6 nm	Cell motility, cytokinesis, muscle contraction
Intermediate Filaments	~10 nm	Mechanical strength, nuclear lamina

6. Transport Across the Cell Membrane

Diffusion (passive): Fat-soluble substances (O₂, CO₂, alcohol) pass freely through the bilayer. Water-soluble ions and molecules require channels.
Active transport: Protein pumps carry substances against concentration gradients, requiring ATP.
Endocytosis:
- Pinocytosis: Ingestion of minute fluid particles and macromolecules via vesicle formation (coated pits with clathrin); requires ATP and Ca²⁺.
- Phagocytosis: Ingestion of large particles (bacteria, dead cells) by macrophages and white blood cells; opsonization by antibodies facilitates this process.
Exocytosis: Secretory vesicles fuse with the cell membrane to release contents.

7. Cell Differentiation

Definition

Differentiation refers to the changes in physical and functional properties of cells as they proliferate — predominantly expressing specific gene sets that mediate specialized cytoplasmic activities, usually with corresponding shape changes.

"Most cells of the fetus undergo a specialization process called differentiation in which they predominantly express sets of genes that mediate specific cytoplasmic activities, becoming efficiently organized in tissues with specialized functions and usually changing their shape accordingly." — Junqueira's Basic Histology, 17e

Mechanism: Selective Gene Repression

Differentiation does not result from loss of genes, but from selective repression of different gene promoters. Electron micrographs show that certain DNA segments wound around histone cores become so condensed that they no longer uncoil to form RNA. At a certain stage, the cell produces a regulatory protein that permanently represses a select group of genes.

Embryological Induction

Parts of the embryo control the differentiation of adjacent cells:

The primordial chordamesoderm (primary organizer) forms a mesodermal axis with segmentally arranged somites that induces formation of essentially all organs.
Developing eye vesicles contact head ectoderm → ectoderm thickens into a lens plate → folds inward to form the lens of the eye.

Specialized Cell Types by Function

General Cellular Activity	Specialized Cell(s)
Movement/contraction	Muscle cells
Form tight junctions	Epithelial cells
Synthesize extracellular matrix	Fibroblasts, osteoblasts, chondrocytes
Convert stimuli to action potentials	Sensory neurons
Phagocytosis	Macrophages, neutrophils
Hormone secretion	Endocrine cells

— Junqueira's Basic Histology, 17e (Table 2-1)

8. Hematopoietic Cell Differentiation (Classic Example)

The hematopoietic system provides the most studied model of cell differentiation in adult life:

Hematopoiesis — All Blood Cells from One Stem Cell:

Hematopoiesis: HSC differentiates into myeloid and lymphoid lineages producing all blood cell types

Revised Hierarchical Model:

Revised human hematopoiesis model — LT-HSC → MPP → CMP/CLP → all mature blood cell lineages

The Long-Term Hematopoietic Stem Cell (LT-HSC) self-renews and gives rise to:

MPP (Multipotent Progenitor) →
- CMP (Common Myeloid Progenitor) → MEP → Erythrocytes, Platelets; GMP → Granulocytes, Monocytes, Dendritic cells
- CLP (Common Lymphoid Progenitor) → T cells, B cells, NK cells

9. Apoptosis: Programmed Cell Death

The complement to differentiation and proliferation is apoptosis — an orderly, programmed cell death that:

Is initiated by activation of caspases (proteases stored as inactive procaspases)
Causes cell shrinkage, cytoskeletal disassembly, and membrane alteration
Results in phagocytosis of the cell before leakage of contents
Does not cause inflammation (unlike necrosis)

Apoptosis is essential during tissue remodeling in development. Even in adults, billions of cells die each hour in tissues such as the bone marrow and gut epithelium.

Contrast with Necrosis:

Necrosis = acute injury → cells swell and burst → membrane integrity lost → contents spill → inflammation → neighboring cell injury.
Apoptosis = controlled → no inflammation → neighboring cells remain healthy.

Summary Table: Major Cell Organelles

Organelle	Membrane?	Key Function
Plasma membrane	Yes	Selective barrier, transport, signaling
Nucleus	Yes (double)	DNA storage, transcription, replication
Rough ER	Yes	Protein synthesis (ribosomes)
Smooth ER	Yes	Lipid synthesis, detoxification
Golgi apparatus	Yes	Protein processing, packaging, secretion
Mitochondria	Yes (double)	ATP production (oxidative phosphorylation)
Lysosomes	Yes	Intracellular digestion
Peroxisomes	Yes	Fatty acid oxidation, H₂O₂ detoxification
Ribosomes	No	Protein synthesis
Cytoskeleton	No	Structure, motility, transport

Sources: Guyton and Hall Textbook of Medical Physiology | Junqueira's Basic Histology, Text and Atlas, 17e | Harper's Illustrated Biochemistry, 32e

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