Eukaryotic Cell Ultrastructure: Nucleus and Endoplasmic Reticulum

Spec Mapping — OCR H420 Module 2.1.1 — Cell structure, content statements covering the ultrastructure of eukaryotic organelles, specifically the nucleus, nucleolus, and rough and smooth endoplasmic reticulum (refer to the official OCR H420 specification document for exact wording). This lesson is the foundation for the protein-production-and-secretion synthesis later in the course, and is examined synoptically with module 6.1 (cellular control / gene expression) on Paper 3.

Understanding the detailed ultrastructure of eukaryotic organelles is at the heart of OCR module 2.1.1. This lesson examines the nucleus, the nucleolus, the nuclear envelope, and the endoplasmic reticulum (both rough and smooth), explaining how their structures are suited to their functions. Because A-Level depth demands precise terminology, you should learn the molecular-level features summarised here.

The systematic dissection of the eukaryotic cell into discrete organelles is one of the central achievements of twentieth-century biology, and its key practitioners are still named in modern exam questions. George Palade at the Rockefeller Institute developed cell-fractionation techniques in the 1950s and traced the secretory pathway from the rough endoplasmic reticulum through the Golgi to the cell surface — work for which he shared the 1974 Nobel Prize. Christian de Duve discovered lysosomes through differential centrifugation and identified them as the cell's digestive compartment. The endosymbiotic theory of Lynn Margulis (1967) re-interpreted the double-membraned mitochondria and chloroplasts as engulfed prokaryotes — a paradigm shift that explains the 70S ribosomes and circular DNA those organelles still carry.

Key Definitions:

Ultrastructure — the detailed three-dimensional organisation of a cell as revealed by electron microscopy.

Organelle — a discrete subcellular structure with a specific function.

Eukaryotic cell — a cell possessing a membrane-bound nucleus and membrane-bound organelles.

SVG cross-section: nucleus and ER continuity

The diagram makes one crucial point explicit: the outer membrane of the nuclear envelope is physically continuous with the rough endoplasmic reticulum (visible as the studded membrane to the right). This is why mRNA emerging through a nuclear pore can begin translation on a ribosome that is already docked on the RER within micrometres of its exit point — the spatial economy is exquisite.

The Nucleus

The nucleus is usually the largest organelle in a eukaryotic cell, typically 5–10 µm in diameter, and is easily visible under a light microscope. It contains almost all of the cell's genetic material in the form of chromatin — a complex of DNA wound around histone proteins.

Functions of the Nucleus

Stores genetic information as DNA in the form of chromosomes.
Controls cell activity by regulating which genes are transcribed to mRNA.
Site of DNA replication during S phase of the cell cycle.
Site of transcription — production of messenger RNA (mRNA) from DNA template.
Contains the nucleolus, which manufactures ribosomal RNA (rRNA) and assembles ribosomal subunits.

The Nuclear Envelope

The nucleus is enclosed by a double membrane known as the nuclear envelope:

Both membranes are phospholipid bilayers, about 7 nm thick each, separated by a perinuclear space of around 20–40 nm.
The outer nuclear membrane is continuous with the rough endoplasmic reticulum (RER) and is often studded with ribosomes.
The inner nuclear membrane is lined by the nuclear lamina, a meshwork of intermediate-filament proteins (lamins) that provides structural support.
The envelope is perforated by nuclear pores, protein-lined channels approximately 100 nm in diameter.

Nuclear Pores

Nuclear pores are complex structures composed of around 30 different nucleoporin proteins, collectively forming the nuclear pore complex (NPC). They regulate the passage of molecules between the nucleus and cytoplasm:

Small molecules (ions, metabolites, up to ~40 kDa) diffuse freely.
Large molecules (proteins, RNA, ribosomal subunits) are actively transported through the NPC, requiring signal sequences and energy.
Nuclear pores allow mRNA to exit the nucleus for translation and allow proteins required in the nucleus (e.g., histones, transcription factors, DNA and RNA polymerases) to enter.

Chromatin and Chromosomes

Inside the nucleus, DNA is associated with histone proteins to form chromatin. During interphase, chromatin exists in two forms:

Euchromatin — loosely packed, transcriptionally active.
Heterochromatin — tightly packed, transcriptionally inactive; often seen as darker regions at the nuclear periphery under TEM.

At cell division, chromatin condenses into the visible rod-like structures known as chromosomes. Humans have 46 chromosomes (23 pairs) per somatic cell. Each chromosome consists of a single, linear DNA molecule wrapped around nucleosomes (histone octamers).

The Nucleolus

Within the nucleus, a densely staining region known as the nucleolus is visible under both light and electron microscopy. A typical cell has one or two nucleoli, each approximately 1–3 µm across.

Functions of the Nucleolus

Synthesises ribosomal RNA (rRNA) by transcription of rRNA genes on special chromosomal regions called nucleolar organiser regions (NORs).
Assembles ribosomal subunits by combining rRNA with ribosomal proteins imported from the cytoplasm. The large (60S) and small (40S) subunits are then exported separately through nuclear pores to the cytoplasm, where they combine during translation to form functional 80S ribosomes.
Involved in regulation of the cell cycle and cellular stress responses.

Key Point: Cells that secrete large amounts of protein (e.g., pancreatic acinar cells, plasma cells) have prominent nucleoli because they must produce huge numbers of ribosomes.

Endoplasmic Reticulum (ER)

The endoplasmic reticulum is an extensive, continuous network of flattened membrane-bound sacs and tubules called cisternae. The lumen (interior) of the ER is distinct from the cytosol. There are two types of ER, distinguishable in electron micrographs by the presence or absence of ribosomes.

Rough Endoplasmic Reticulum (RER)

Studded on its cytosolic face with 80S ribosomes, giving it a granular appearance under TEM.
Continuous with the outer nuclear membrane.
Arranged as flattened, stacked cisternae.

Function

Synthesis of proteins for secretion, for incorporation into membranes, or for use in lysosomes.
As a ribosome begins to synthesise a protein destined for secretion, a signal sequence at the start of the growing polypeptide directs the ribosome to the RER surface.
The ribosome docks onto a translocon channel in the RER membrane.
The growing polypeptide enters the lumen, where it undergoes folding (assisted by chaperone proteins) and early glycosylation (addition of sugar groups to form glycoproteins).
Proteins are then packaged into transport vesicles that bud off the RER and move to the Golgi apparatus.

Cells with Abundant RER

Pancreatic cells (secreting digestive enzymes).
Plasma cells (B lymphocytes secreting antibodies).
Liver hepatocytes (secreting albumin and other plasma proteins).

Smooth Endoplasmic Reticulum (SER)

Lacks ribosomes, giving it a smooth appearance under TEM.
Typically more tubular than RER.

Functions

Lipid synthesis, including phospholipids for new membranes and steroid hormones.
Carbohydrate metabolism, including synthesis and storage of glycogen.
Detoxification of drugs, alcohol, and other xenobiotics — particularly in liver cells, where the SER contains enzymes such as cytochrome P450 that modify hydrophobic toxins so they can be excreted.
Calcium storage in muscle cells, where specialised SER called the sarcoplasmic reticulum releases Ca²⁺ to trigger contraction.

Cells with Abundant SER

Liver hepatocytes (detoxification, glycogen metabolism).
Testes Leydig cells and ovarian cells (steroid hormone synthesis).
Skeletal and cardiac muscle cells (calcium storage in sarcoplasmic reticulum).

RER vs SER: side-by-side comparison

Feature	Rough ER	Smooth ER
Ribosomes on cytosolic face?	Yes (80S)	No
Shape under TEM	Flattened stacked cisternae	Interconnected tubules
Main biosynthetic role	Protein synthesis (secretory, membrane, lysosomal)	Lipid and steroid synthesis
Folding / quality control role	Yes (chaperones, disulfide isomerase)	No
Glycosylation?	Yes (N-linked, asparagine)	No
Detoxification role?	No	Yes (cytochrome P450 enzymes)
Calcium storage?	No	Yes (sarcoplasmic reticulum in muscle)
Continuity with outer nuclear membrane?	Direct	Indirect (via RER)
Cells with abundant examples	Plasma cells, pancreatic acinar, hepatocytes	Liver hepatocytes, Leydig cells, muscle

The two systems share the same membrane chemistry and continuous lumen, but their cytosolic surface architecture (ribosome-studded vs smooth) and luminal enzyme content (chaperones/oxidoreductases vs lipid-biosynthesis enzymes) differ markedly. The ratio of RER to SER in a cell is therefore a reliable indicator of whether the cell's primary output is protein (high RER:SER) or lipid/steroid/detoxification work (high SER:RER).

Relationship Between Nucleus and ER

The outer nuclear membrane is physically continuous with the RER. This direct continuity is significant because:

mRNA exiting the nucleus through nuclear pores can quickly find nearby ribosomes — whether free in the cytosol or already attached to RER.
Newly synthesised membrane proteins and secretory proteins can be inserted directly into or translocated across the ER membrane without a separate transport step.

flowchart LR
    N[Nucleus]:::n --> P[Nuclear pore]
    P --> M[mRNA in cytosol]
    M --> R80[80S ribosome on RER]
    R80 --> ER[RER lumen: polypeptide folds]
    ER --> V[Transport vesicle buds off]
    N -. continuous membrane .- OM[Outer nuclear membrane]
    OM -. continuous with .- ER
    classDef n fill:#fce,stroke:#333

Ultrastructure Comparison Table

Feature	Nucleus	RER	SER
Membranes	Double (envelope)	Single (cisternal)	Single (tubular)
Continuous with outer nuclear membrane?	—	Yes	Yes (indirectly via RER)
Ribosomes on cytosolic face?	No (but outer membrane sometimes has some)	Yes	No
Main function	DNA storage, transcription, rRNA synthesis	Protein synthesis for secretion/membranes	Lipid synthesis, detoxification, calcium storage
Structural appearance (TEM)	Largest organelle, with dark nucleolus	Flattened, stacked cisternae studded with dots	Interconnected tubules, smooth membrane

Common Exam Mistakes

Saying the nucleus is surrounded by a single membrane. It is a double membrane (the nuclear envelope).
Confusing nucleolus with nucleus. The nucleolus is a small, dense region within the nucleus; it is not the same thing.
Claiming that the nuclear pores are simple holes. They are protein complexes that selectively control traffic in and out.
Failing to link RER structure to function. Always explicitly connect: "RER has ribosomes on its surface → site of protein synthesis for secretion."
Confusing RER with SER functions. RER = protein; SER = lipid, steroid, detoxification, calcium.
Stating that RER synthesises all proteins. Ribosomes in the cytosol synthesise proteins that remain inside the cell (cytosolic proteins); only proteins destined for secretion, membranes, or lysosomes are made on the RER.

Exam Tip: If a cell has many mitochondria and extensive RER and a large, prominent nucleolus, it is almost certainly a highly secretory cell (e.g., pancreatic acinar cell or plasma cell). Recognising this pattern earns easy marks in "suggest what type of cell this is" questions.

Eukaryotic Cell Ultrastructure: Nucleus and ER