Evidence-based physiotherapy and rehabilitation resources
Editorial & review policy
Evidence-based physiotherapy and rehabilitation resources
Editorial & review policyHuman Physiology · Foundations
Every treatment you give is received by cells. Training builds mitochondria, load is read by the cytoskeleton, and immobility tells cells to break themselves down. This page is the map of where those changes happen.
Part 1 · Foundations · Chapter 2 of 47
By the end of this page you should be able to:
A muscle becomes stronger because its fibres build more contractile protein. It gains endurance because its fibres build more mitochondria. A tendon remodels because its fibroblasts lay down new collagen in response to load.
Each of those changes happens inside cells. When you choose a load, a number of repetitions or a rest period, you are sending a signal that cells will read. Knowing the parts of the cell tells you what that signal can and cannot change.
The adult body contains trillions of cells of a few hundred types. Almost all share the same basic plan: a membrane around the outside, a nucleus holding the genes, and a cytoplasm full of specialised structures called organelles.
Figure 1 · A typical human cell
| Organelle | Main job | Where you will meet it clinically |
|---|---|---|
| Cell membrane | Barrier, transport, signalling, adhesion | Nerve and muscle excitability; drug and hormone receptors |
| Nucleus | Holds DNA; controls which proteins are made | Muscle fibres have many nuclei; adding nuclei supports hypertrophy |
| Ribosomes | Build proteins from mRNA | Protein synthesis after resistance training |
| Rough endoplasmic reticulum | Makes proteins for export or the membrane | Fibroblasts making collagen during tissue repair |
| Smooth endoplasmic reticulum | Lipid synthesis; calcium storage | In muscle, the sarcoplasmic reticulum stores the calcium that triggers contraction |
| Golgi apparatus | Modifies, labels and sorts proteins | Processing of collagen and secreted proteins |
| Mitochondria | Make most of the cell’s ATP aerobically | Endurance, fatigue resistance, effects of training and disuse |
| Lysosomes | Digest worn-out parts and engulfed material | Clearing damaged organelles; tissue breakdown after injury |
| Peroxisomes | Break down fatty acids and hydrogen peroxide | Lipid metabolism |
| Cytoskeleton | Shape, movement, internal transport, load sensing | Mechanotransduction; axonal transport in nerves |
In 1972 Singer and Nicolson proposed the fluid mosaic model. The membrane is a double layer of phospholipid in which proteins are embedded like tiles in a moving mosaic [1].
Each phospholipid has a water-loving (polar) head and two water-avoiding (non-polar) tails. In water they arrange themselves with the heads outward and the tails meeting in the middle. That middle layer is oily, so ions and water-soluble molecules cannot pass through it freely [1].
Figure 2 · The fluid mosaic membrane
Cholesterol sits among the tails and steadies the membrane. Carbohydrate chains attached to proteins and lipids on the outer surface form the glycocalyx, which helps cells recognise one another.
Everything the membrane does beyond being a barrier is done by its proteins. They fall into a small number of working groups.
| Membrane protein | What it does | Example |
|---|---|---|
| Channel | A water-filled pore that lets specific ions through, often opening and closing (gated) | Voltage-gated sodium channels in nerve and muscle |
| Carrier (transporter) | Binds a substance and changes shape to move it across | Glucose transporters in muscle |
| Pump | A carrier that uses ATP to move ions against their gradient | The sodium–potassium pump |
| Receptor | Binds a signal molecule and triggers a response inside | Acetylcholine receptors at the neuromuscular junction; insulin receptors |
| Enzyme | Speeds a reaction at the membrane surface | Enzymes on the gut lining that finish digestion |
| Adhesion and linker proteins | Attach the cell to neighbours or to the matrix | Integrins linking cells to collagen |
Chapter 3 shows how channels, carriers and pumps move substances across the membrane. Part 2 builds the nerve impulse from them.
The nucleus holds the DNA, wrapped around proteins as chromatin. A gene is a stretch of DNA that codes for a protein. To make that protein, the cell copies the gene into messenger RNA (transcription), which leaves the nucleus through nuclear pores.
In the cytoplasm, ribosomes read the mRNA and join amino acids in the right order (translation). The nucleolus is the dense region of the nucleus where ribosomes are assembled.
Figure 3 · From gene to working protein
Proteins for use inside the cell are made on free ribosomes. Proteins for export, for the membrane or for lysosomes are made on the rough endoplasmic reticulum. They then pass through the Golgi apparatus, where they are modified and sorted, and leave in vesicles.
Skeletal muscle fibres are unusual in having hundreds of nuclei each. Each nucleus serves a region of the fibre, which is one reason why adding nuclei from satellite cells supports large increases in fibre size.
Mitochondria make most of the cell’s ATP by aerobic metabolism. Fuel from glucose and fat is broken down, and its energy is used on the folded inner membrane, the cristae, to make ATP. This process is oxidative phosphorylation, and it needs oxygen.
Mitochondria have their own small circle of DNA, inherited from the mother. They divide, fuse and are removed independently of the cell around them. That makes them unusually responsive to how a tissue is used.
Figure 4 · Mitochondria respond to how a muscle is used
In 1967 Holloszy trained rats on a treadmill and measured their leg muscles. The mitochondrial capacity to use oxygen, and the activity of respiratory enzymes, roughly doubled [3]. This was the first clear evidence that endurance training changes muscle at the level of the organelle.
Later work has shown how. Exercise activates signalling, centred on a regulator called PGC-1α, that builds new mitochondria and improves the systems that keep them in good repair [4]. Damaged mitochondria are tagged, engulfed and broken down in lysosomes, a process called mitophagy [5].
Disuse starts some of the same signals, but the outcome is the opposite: fewer mitochondria, of poorer quality [4]. Ageing also impairs mitochondrial quality control, and both endurance and resistance exercise help to maintain it [7].
Lysosomes are membrane sacs of digestive enzymes that work best in acid conditions. They break down material the cell has engulfed and parts of the cell itself that are worn out.
Autophagy (“self-eating”) is the routine recycling of the cell’s own components. It is not only destructive. By clearing damaged proteins and organelles, it keeps the cell working, and exercise increases both mitophagy and the production of new lysosomes in muscle [5].
Peroxisomes are smaller sacs that break down very long fatty acids and neutralise hydrogen peroxide.
The cytoskeleton is a network of protein filaments that gives the cell its shape, moves things around inside it, and connects it to its surroundings. It has three types of filament.
| Filament | Approximate width | Main roles |
|---|---|---|
| Microfilaments (actin) | about 7 nm | Cell shape and movement; in muscle, the thin filaments of contraction |
| Intermediate filaments | about 10 nm | Tensile strength; anchor cells at desmosomes (keratin in skin, desmin in muscle) |
| Microtubules | about 25 nm | Tracks for transport inside the cell, including along axons; form the spindle in cell division |
Because the cytoskeleton is physically linked through the membrane to the surrounding matrix, mechanical load applied to a tissue reaches the inside of its cells. Cells sense this and respond by changing which genes they use. This is mechanotransduction [6].
Figure 5 · How load becomes tissue
Khan and Scott use the term mechanotherapy for exercise prescribed specifically to promote repair through this process [6]. They describe three steps: mechanical coupling of load to the cell, communication between cells, and an effector response in which new tissue is made.
This is the physiology behind loading programmes for tendinopathy, graded loading after muscle strain, and weight-bearing after fracture.
| Junction | What it does | Where it matters |
|---|---|---|
| Tight junction | Seals neighbouring cells so fluid cannot leak between them | Gut lining; the blood–brain barrier |
| Adherens junction | Links the actin cytoskeletons of neighbouring cells | Epithelia; heart muscle |
| Desmosome | Spot-weld linking intermediate filaments; resists pulling apart | Skin; heart muscle intercalated discs |
| Gap junction | Channels that let ions pass directly between cells | Spreading the impulse through heart and smooth muscle |
| Hemidesmosome and focal adhesion | Anchor cells to the basement membrane and matrix via integrins | Skin; tendon and other load-bearing tissues |
Cells reproduce by mitosis: the DNA is copied and the cell divides into two identical daughters. Tissues differ greatly in how readily their cells do this, and that decides how they heal.
| Tissue type | Ability to divide | Examples | Healing consequence |
|---|---|---|---|
| Continuously dividing | Constantly replaced | Skin surface, gut lining, blood-forming marrow | Heals quickly, often without scar |
| Quiescent (stable) | Normally resting; divide when injured | Liver, fibroblasts, bone cells, smooth muscle | Regenerates if the framework is intact |
| Largely non-dividing | Little or no division in adults | Most neurons; heart muscle; skeletal muscle fibres (rely on satellite cells) | Lost cells are replaced by scar, or not at all |
| Apoptosis | Necrosis | |
|---|---|---|
| What it is | Programmed, orderly cell death | Uncontrolled death after severe injury |
| Cell appearance | Shrinks and breaks into tidy fragments | Swells and bursts |
| Inflammation | None; fragments quietly removed | Contents spill out and trigger inflammation |
| Examples | Normal turnover, development, removing damaged cells | Infarction after loss of blood supply, crush injury, burns |
The neurons lost in a stroke and the heart muscle lost in an infarct are not replaced. Recovery after stroke depends on the surviving brain reorganising, which is the basis of neurorehabilitation and is covered in the nervous system chapters.
| What you measure | What it reflects at cell level |
|---|---|
| Endurance tests (six-minute walk, repetitions to fatigue) | Mitochondrial capacity and oxygen delivery |
| Strength and muscle size | Contractile protein and number of nuclei per fibre |
| Response to loading over weeks | Mechanotransduction and tissue remodelling |
| Loss of capacity after bed rest or casting | Protein breakdown and reduced mitochondrial content |
Practical skill · explaining load to a patient
Patients often fear that loading will damage a healing tissue. A one-sentence explanation helps: “Your cells need the right amount of load as a signal to rebuild; too little and they break down, too much too soon and they are injured.” This is mechanotherapy in plain words [6].
Describe the structure and functions of the cell membrane. Add a note on membrane proteins.
The membrane is drawn as a uniform fluid bilayer, and mitochondria as fixed numbers of separate power stations.
The fluid mosaic model still holds, but membranes are now known to be crowded and organised into domains. The cytoskeleton and matrix fence in many components and limit how far they move [2].
Mitochondria are now understood as a dynamic network. They are built, fused, divided and removed in response to use, and this quality control is as important as their number [4, 5, 7].
Learn the classic model for the exam, then add one sentence on domains and one on mitochondrial quality control. Both connect cell biology directly to why exercise works.
10 questions on this page. Tap one to see the answer and the reasoning.
Answer: (B) Singer and Nicolson described globular proteins embedded in a fluid phospholipid bilayer [1].
Answer: (B) Polar groups face the water; the non-polar tails form a hydrophobic interior that ions cannot easily cross [1].
Answer: (B) Lipid rafts, protein complexes and cytoskeletal fences limit lateral movement; the basic model still stands [2].
Answer: (C) Oxidative phosphorylation on the inner mitochondrial membrane supplies most ATP during sustained work [3, 4].
Answer: (C) Treadmill training markedly increased mitochondrial oxygen uptake and respiratory enzyme activity in skeletal muscle [3].
Answer: (B) Disuse produces similar early signals to exercise but ends with reduced mitochondrial quality and content [4].
Answer: (B) Poorly functioning mitochondria are engulfed in autophagosomes and degraded in lysosomes; exercise enhances this [5].
Answer: (B) Khan and Scott define it as cells sensing and responding to load, the basis of mechanotherapy [6].
Answer: (A) Integrins anchor the cell to the matrix and pass mechanical signals inward [6].
Answer: (B) Ageing disturbs biogenesis and quality control; endurance and resistance exercise both help maintain mitochondrial health [7].
Key takeaways
| Source | Why it earns its place |
|---|---|
| Alberts B et al. — Molecular Biology of the Cell | The standard reference on every structure on this page |
| Hall JE, Hall ME — Guyton and Hall Textbook of Medical Physiology | Concise physiology of the cell and its organelles |
| Khan KM, Scott A — British Journal of Sports Medicine, 2009 | The short, illustrated case for mechanotherapy [6] |
| Slavin MB et al. — Am J Physiol Cell Physiol, 2022 | Current account of mitochondrial adaptation to use and disuse [4] |
Reviewed by the Physiotherapist India Team. · Human Physiology contents