HookThe cells that never stopped dividing
In 1951 a Baltimore doctor took a sample of cells from a cervical tumour belonging to a 31-year-old woman named Henrietta Lacks. Every human cell line grown before had died within days. Hers did not. They doubled roughly every 24 hours and simply kept going — and today, seventy years and an estimated 50 million tonnes of cultured cells later, 'HeLa' cells are still dividing in laboratories on every continent. They helped test the polio vaccine, went up in the first space missions, and appear in tens of thousands of papers. Henrietta Lacks died months after that sample was taken; her cells never got the memo.
Why would cells refuse to stop? Because in a cancer cell the brakes on the cell cycle are broken — the checkpoint proteins that normally halt a damaged cell are disabled, so mitosis runs without limit. That single fact is the spine of this topic. To understand it you need to know what is inside a cell (its organelles), how it differs from a bacterium or a virus, how we see and separate structures far too small for the eye, how the cell cycle and mitosis are meant to be controlled, how substances cross the membrane that bounds every cell, and how your immune system recognises a cell that has gone wrong. Every one of those threads runs back to Henrietta Lacks's runaway cells.
ModelInside a eukaryotic cell — the organelles and a protein's journey
Eukaryotic cells — of animals, plants, fungi and protoctista — are defined by membrane-bound organelles, each a compartment specialised for a job. The nucleus is wrapped in a double membrane, the nuclear envelope, pierced by nuclear pores that let large molecules such as mRNA out; inside sit the DNA (as chromatin) and the nucleolus, which makes ribosomes. Mitochondria have a double membrane whose inner layer folds into cristae surrounding a fluid matrix — the site of aerobic respiration and most ATP synthesis. Chloroplasts, in plants and algae, hold stacks of thylakoid membranes (grana) in a stroma and carry out photosynthesis.
The protein-export system is a favourite exam story. Ribosomes (the eukaryotic type is 80S) build proteins; those studding the rough endoplasmic reticulum feed new proteins into its membranes for folding and transport, while smooth endoplasmic reticulum makes lipids. Vesicles carry proteins to the Golgi apparatus, which modifies, packages and labels them — for instance adding carbohydrate to make glycoproteins — and pinches off vesicles, including lysosomes full of hydrolytic enzymes. A secreted protein's route is examinable as a sequence: ribosome on rough ER, then vesicle, then Golgi, then vesicle to the cell-surface membrane, then release by exocytosis.
Plant cells add three features: a cellulose cell wall for support, a large permanent vacuole bounded by a tonoplast, and chloroplasts. Fungal walls are made of chitin instead. Knowing which organelle does what, and being able to relate its structure to its function, is the bedrock of the whole paper.
ModelProkaryotes and viruses — simpler, smaller, and not even alive
Prokaryotic cells — bacteria — are much smaller (about 1 to 5 micrometres) and far simpler. They have no nucleus and no membrane-bound organelles. Their DNA is a single circular molecule floating free in the cytoplasm and, crucially, not wound around histone proteins. Their ribosomes are the smaller 70S type, and their cell wall is made of murein (a peptidoglycan), not cellulose. Many carry extras: a protective capsule, one or more plasmids (small DNA rings holding genes such as antibiotic resistance) and flagella for movement. Every distinction from a eukaryote is a potential compare-and-contrast mark.
Viruses are not cells at all — they are acellular and non-living. A virus has no cytoplasm, no organelles and no ribosomes; it is simply genetic material (either DNA or RNA) inside a protein coat called a capsid, with attachment proteins on the outside. Some, such as HIV, also have a lipid envelope taken from a previous host cell. The attachment proteins are shape-specific: HIV's bind the CD4 receptor on human helper T cells, which is exactly why that virus targets the immune system. Because a virus has no machinery of its own, it can only replicate by hijacking a living host cell — the reason antibiotics, which attack bacterial structures, do nothing to a virus.
DataSeeing the invisible — microscopy, resolution and cell fractionation
Two ideas are constantly confused. Magnification is how many times bigger the image is than the object. Resolution is the smallest distance apart two points can be while still appearing separate — and it is fixed by the wavelength of whatever you illuminate with. A light microscope uses light (wavelength hundreds of nanometres) and resolves to about 200 nm; a transmission electron microscope (TEM) fires electrons, whose far shorter wavelength resolves to around 0.1 nm and reveals internal ultrastructure; a scanning electron microscope (SEM) gives a lower-resolution three-dimensional surface view. Electron microscopes must work in a vacuum on dead, treated specimens, so artefacts are a real risk.
The formula is the workhorse: magnification = image size divided by actual size. Rearrange it with the 'I A M' triangle — Image equals Actual times Magnification. The only reliable way to lose marks is to divide two lengths measured in different units, so convert everything to the same unit first (1 mm = 1000 micrometres = 1000000 nanometres), and express large magnifications in standard form.
To study organelles in bulk you separate them by cell fractionation. First homogenise the tissue in a solution that is cold (to slow hydrolytic enzymes that would digest organelles), isotonic (the same water potential, so organelles neither burst nor shrivel by osmosis) and buffered (constant pH, so proteins do not denature). Filter out debris, then spin the filtrate in an ultracentrifuge at increasing speeds: the densest organelles pellet first (nuclei), then mitochondria and chloroplasts, then endoplasmic reticulum, and finally ribosomes.
An electron micrograph shows a mitochondrion 42 mm long. Its scale bar, labelled 2 micrometres, measures 20 mm on the page. Find the magnification and the mitochondrion's real length. First the magnification, from the scale bar — convert to one unit (20 mm = 20000 micrometres): \[M = \dfrac{\text{image}}{\text{actual}} = \dfrac{20000}{2} = 10000\times = 1 \times 10^{4}.\] Now the real mitochondrion, rearranging to actual = image divided by magnification (42 mm = 42000 micrometres): \[\text{actual} = \dfrac{42000}{10000} = 4.2\ \text{micrometres}.\] That is a believable size for a mitochondrion (they run about 0.5 to 10 micrometres). Every mark here is a units mark: mixing millimetres and micrometres is the classic slip.
MechanismThe cell cycle, mitosis and the brakes that fail in cancer
Most of a dividing cell's life is interphase, split into three parts: G1 (the cell grows and makes organelles and proteins), S (the DNA is replicated so each chromosome becomes two identical sister chromatids joined at a centromere) and G2 (more growth and checking). Then comes mitosis, nuclear division, in four stages you must sequence. In prophase the chromosomes condense and become visible, the nuclear envelope breaks down and spindle fibres form. In metaphase the chromosomes line up on the equator, attached to spindle fibres by their centromeres. In anaphase the centromeres split and the spindle pulls sister chromatids to opposite poles. In telophase the chromosomes decondense and two nuclear envelopes re-form. Finally cytokinesis divides the cytoplasm into two genetically identical daughter cells.
Mitosis is how organisms grow, replace damaged cells and reproduce asexually — and because the daughters are genetically identical, it produces no variation. The cycle is policed at checkpoints by regulatory proteins that halt a cell with damaged or unreplicated DNA. When the genes for those proteins mutate, control is lost: cells divide uncontrollably to form a tumour. That is precisely what happened in Henrietta Lacks's cells, and it explains why many cancer drugs, and radiotherapy, are aimed at cells in the act of dividing.
DataRequired practical 2 — root-tip squashes and the mitotic index
This practical makes the stages of mitosis visible and quantifies how fast a tissue divides. Cut the last few millimetres from a growing root tip (garlic or onion work well), where mitosis is common. Hydrolyse the tissue in warm dilute hydrochloric acid to separate the cells, then stain with a DNA stain such as toluidine blue or acetic orcein, which binds the chromosomes and turns them dark. Place the tip on a slide, add a coverslip and squash it gently to spread the cells into a single layer, then view — low power to find the dividing region, high power to identify stages.
The quantitative output is the mitotic index: the proportion of cells that are in mitosis (chromosomes visible) out of the total cells counted. Because it is a proportion, it estimates how much of the cell cycle is spent dividing, and a raised index in a tissue sample can flag rapid, possibly cancerous, growth. Control variables include the region of root sampled, staining time and the observer's criteria for 'in mitosis'; counting several fields and taking a mean reduces the effect of an unrepresentative patch. The main error is subjectivity — deciding whether a faint cell counts — so agreeing clear criteria and, ideally, counting blind improves reliability.
A student counts 50 cells in a field of view and finds 8 with condensed, visible chromosomes — cells in mitosis. The mitotic index is the fraction in mitosis: \[\text{mitotic index} = \dfrac{8}{50} = 0.16.\] If the whole cell cycle in this tissue lasts 24 hours, the time spent in mitosis is roughly the index times the cycle length: \(0.16 \times 24 = 3.84\) hours, about 3 hours 50 minutes. Note the index is a proportion between 0 and 1 (or a percentage) — never a count. Counting only one field is the weakness; averaging several fields gives a value you can trust.
MechanismCrossing the membrane — four routes in and out
Every cell is wrapped in a cell-surface membrane described by the fluid-mosaic model: a fluid phospholipid bilayer studded with proteins, cholesterol (which stabilises fluidity) and glycoproteins. Substances cross it four ways. Simple diffusion is the net, passive movement of small, non-polar molecules such as oxygen down a concentration gradient. Facilitated diffusion moves polar or charged particles, still passively and down their gradient, but through channel or carrier proteins because they cannot cross the hydrophobic core alone.
Osmosis is the passive movement of water across a partially permeable membrane, from a higher (less negative) to a lower (more negative) water potential. Water potential, symbol psi, is measured in kilopascals; pure water is defined as 0 kPa, the maximum, and adding solute always makes it negative. In plant cells it splits into two: \(\Psi = \Psi_s + \Psi_p\), the (negative) solute potential plus the (usually positive) pressure potential from the cell wall pushing back.
Active transport moves substances against their concentration gradient using a carrier protein and energy from ATP — how root hair cells absorb mineral ions from dilute soil water. Co-transport couples the two: in the ileum, a sodium-potassium pump uses ATP to keep sodium low inside the epithelial cell, so sodium floods back in through a co-transporter, dragging glucose or amino acids in with it, even against the glucose gradient. The rate of all of these rises with surface area, the steepness of the gradient and (for the protein-dependent routes) the number of transport proteins.
DataRequired practicals 3 and 4 — water potential and membrane permeability
Required practical 3 finds the water potential of plant tissue using a dilution series and a calibration curve. Make a range of sucrose concentrations (for example 0.0, 0.2, 0.4, 0.6, 0.8 and 1.0 mol per cubic decimetre) by serial dilution, cut potato cylinders of equal size, blot and weigh each, then leave one in each concentration for a fixed time before blotting and reweighing. The independent variable is sucrose concentration; the dependent variable is the percentage change in mass; controls include tissue source, temperature, time and cylinder size. Plot percentage change against concentration and read off where the line crosses zero — at that concentration there is no net osmosis, so the external solution's water potential equals the tissue's, which you look up from a calibration table. Reporting percentage rather than raw grams lets cylinders of slightly different starting mass be compared fairly.
Required practical 4 investigates what affects the permeability of the cell-surface membrane, usually using beetroot, whose vacuoles are full of red betalain pigment. Cut equal-sized cores, wash off pigment released by cutting, then expose them to your chosen variable — commonly a range of temperatures, or ethanol concentrations. As the membrane is disrupted, pigment leaks out, and you measure how much using a colorimeter: more leakage means a more coloured solution and a higher absorbance. Above roughly 40 to 50 degrees Celsius the phospholipids gain kinetic energy and the membrane proteins denature, so permeability rises sharply. The colorimeter is the key improvement here because it replaces a subjective judgement of colour with an objective number.
In Required practical 3 a potato cylinder starts at 5.2 g and, after 30 minutes in 0.5 mol per cubic decimetre sucrose, weighs 4.68 g. The percentage change in mass is \[\dfrac{m_f - m_i}{m_i} \times 100 = \dfrac{4.68 - 5.2}{5.2} \times 100 = -10\%.\] The cylinder lost mass, so water moved out by osmosis: the sucrose solution had a lower (more negative) water potential than the potato cells, and water always moves down the water-potential gradient. Where the graph of percentage change crosses 0%, mass is unchanged, the solution is isotonic with the tissue, and the two water potentials are equal — that reading, converted with the calibration table, is the answer.
CaseAntigens, cell recognition and the immune response
Your immune system's job is to tell self from non-self, and it does it by reading antigens — molecules, usually proteins, on cell surfaces. Foreign antigens on pathogens, toxins, cancer cells or transplanted tissue all trigger a response. The first, non-specific line includes phagocytosis: a phagocyte engulfs a pathogen into a vesicle (phagosome), which fuses with a lysosome so hydrolytic enzymes digest it; the phagocyte then displays the pathogen's antigens on its surface, becoming an antigen-presenting cell.
The specific response has two arms. In the cellular response, a helper T cell whose receptor is complementary to the presented antigen is selected and activated; it then stimulates phagocytes, cytotoxic T cells (which destroy infected cells) and B cells. In the humoral response, a B cell carrying a complementary antibody binds the antigen and, helped by the T cell, divides by mitosis (clonal expansion) into plasma cells, which pour out antibodies, and memory cells. An antibody is a quaternary-structure protein with a variable region that is complementary to one specific antigen, forming an antigen-antibody complex and clumping pathogens together (agglutination) for easier phagocytosis.
Memory cells explain immunity: a second exposure triggers a faster, larger secondary response before symptoms appear, which is what vaccination exploits by presenting harmless antigens. Pathogens fight back with antigenic variation — changing their surface antigens so old memory cells no longer fit, the reason influenza needs a new jab each year. HIV is the dark mirror of this topic: it infects and destroys helper T cells, so the whole coordinated response collapses and AIDS follows. And monoclonal antibodies — identical antibodies from one clone — put this specificity to work, from targeting drugs at cancer cells to detecting the hormone hCG in a pregnancy test.
VocabularyKey terms the mark scheme pays for
TrapsMisconceptions that cost marks
ExamWhat examiners want
AQA weights this paper towards AO2 application and AO3 analysis, so bare recall is rarely enough. Microscopy maths is guaranteed and generous if you are disciplined: convert image and actual size to the same unit before dividing, use the Image = Actual x Magnification triangle, quote large magnifications in standard form, and give a sensible unit (micrometres for whole organelles, nanometres for membranes). For a scale bar, magnification is the bar's measured length divided by the value it represents.
Process questions are marked on correct sequence and cause. Put the four mitosis stages in order with the key event of each; describe the immune response as an ordered chain from antigen presentation to helper T cell to B cell to plasma and memory cells; and give cell fractionation as homogenise-filter-centrifuge with a reason for each of cold, isotonic and buffered. For membrane transport, always state two things — the direction relative to the concentration gradient, and whether ATP is needed — because those separate diffusion, facilitated diffusion, osmosis and active transport.
Required-practical marks reward method detail, variables and error analysis, so learn them as facts: percentage change in mass and a calibration curve for water potential, a colorimeter for objective pigment measurement, and the mitotic-index calculation. Get the water-potential sign convention right every time (pure water 0, solutions negative, water moves to the more negative value), and when a practical yields numbers, show the calculation and add the one-sentence interpretation that most candidates leave out.