Difficulty: Intermediate | Prerequisites: Energy and bonds (Doc 2), enzyme and metabolism basics (Doc 3)
This material covers how cells are built, how substances cross their membranes, how the cytoskeleton provides structural support and movement, and how cells communicate with their surroundings through the extracellular matrix and junctions. You should be comfortable with electrochemical gradients (Doc 2) and ATP as an energy source (Doc 3) before working through this. These concepts are the mechanical foundation of every organ system: muscles, nerves, kidneys, and glands all depend on the transport and structural principles covered here.
Cell membranes are selectively permeable barriers made of phospholipids and proteins. Substances cross them by passive diffusion, facilitated diffusion, or active transport (which costs energy). The cytoskeleton provides shape and enables movement, while cell junctions and the extracellular matrix hold tissues together and allow communication. Gene regulation (histones, splicing, ubiquitin-proteasome degradation) controls which proteins a cell produces and when.
Lipid rafts
Thickened regions of the plasma membrane enriched in cholesterol, long-chain phospholipids, and proteins with long transmembrane domains. They serve as platforms for signalling.
Integral membrane proteins
Proteins tightly embedded in the membrane, often spanning it entirely (transmembrane proteins).
Peripheral membrane proteins
Proteins loosely attached to the membrane surface through interactions with lipids or integral proteins.
Passive diffusion
Movement of a substance across a membrane without a protein carrier, driven by the concentration gradient alone. Only small, non-polar molecules cross this way.
Facilitated diffusion
Passive transport assisted by a membrane protein (channel or carrier). No energy required; the substance moves down its electrochemical gradient.
Ion channels
Transmembrane proteins that form aqueous pores, allowing ions to flow down their electrochemical gradient. Fast, but not very selective beyond charge and size.
Ligand-gated channels
Ion channels that open when a specific ligand binds (e.g., acetylcholine opening Na+ channels at the neuromuscular junction).
Mechanogated channels
Ion channels that open or close in response to mechanical stress or stretch on the membrane.
Porin
A channel that permits facilitated diffusion of larger molecules. Aquaporins are porins specialised for water.
Aquaporins
Large tetrameric channels that allow rapid passage of water through the plasma membrane.
Permease / carrier protein
A transporter that mediates facilitated diffusion by binding a substrate, changing shape, and releasing it on the other side. Slower and more selective than channels. GLUT proteins (glucose transporters) are the classic example.
Active transport
Protein-mediated movement of a substance against its electrochemical gradient, requiring energy. Primary active transport uses ATP directly. Secondary active transport uses the gradient established by a primary pump.
Primary active transport
Uses chemical energy (ATP) or light directly. The Na+/K+ ATPase and Ca2+ ATPase are key examples.
Secondary active transport
Uses the electrochemical gradient of one molecule (established by primary transport) to drive transport of another molecule against its gradient. Symporters move both in the same direction; antiporters move them in opposite directions.
Electroneutral
A transport process that does not change the net electrical charge across the membrane.
Electrogenic
A transport process that does change the net charge, altering the membrane potential. The Na+/K+ ATPase is electrogenic (3 Na+ out, 2 K+ in = net positive charge moved out).
Membrane potential
The electrical gradient (voltage difference) across a cellular membrane, typically negative inside.
Excitable cells
Cells (neurons, muscle cells) that use rapid changes in membrane potential as communication signals.
Equilibrium potential
The membrane potential at which a specific ion is at electrochemical equilibrium, with no net movement across the membrane.
Reversal potential
The membrane potential at which there is no net ion movement through open ion channels.
Goldman equation
Predicts the resting membrane potential from the distribution and relative permeabilities of multiple ions (typically Na+, K+, and Cl-).
Mitochondria
Organelles that produce ATP via oxidative phosphorylation. Organised as a network or reticulum in many tissues.
Cytoskeleton
The intracellular protein network of microtubules, microfilaments, and intermediate filaments that gives the cell shape and enables movement.
Microfilaments
Polymers of actin used to construct the cytoskeleton and drive cell movement.
Microtubules
Hollow tubes of polymerised tubulin. They form the mitotic spindle, cilia, and flagella, and serve as tracks for motor proteins.
Intermediate filaments
Rope-like proteins (e.g., keratin, vimentin) that provide mechanical strength.
Tubulin
The monomeric protein subunit of microtubules, a dimer of alpha-tubulin and beta-tubulin.
Actin
G-actin monomers polymerise into F-actin filaments. Found in the cytoskeleton (beta/gamma isoforms) and in muscle thin filaments (alpha isoform).
Myosin
ATP-dependent motor proteins that work with actin. The thick filament of muscle is composed of myosin hexamers (two heavy chains, four light chains).
Kinesin
A motor protein that moves cargo along microtubules toward the plus end (typically toward the cell periphery).
Dynein
A motor protein that moves cargo along microtubules toward the minus end (typically toward the cell centre).
Endoplasmic reticulum (ER)
An intracellular membrane network for protein processing (rough ER) and lipid synthesis (smooth ER).
Vesicle
A membrane-bound compartment that buds from the intracellular membrane network, often coated with clathrin, used for transporting cargo.
Pinocytosis
Endocytosis of fluids ("cell drinking").
Phagocytosis
Endocytosis of large particles ("cell eating").
Bulk transport (exocytosis/endocytosis)
Movement of large molecules by fusion of vesicles with the plasma membrane (exocytosis = out; endocytosis = in).
Extracellular matrix (ECM)
The protein and glycosaminoglycan network outside cells, including cartilage, bone, and connective tissue.
Collagen
A trimeric protein of the ECM that forms rigid fibres or durable sheets. The most abundant protein in the body.
Proteoglycans
Molecules composed of protein cores with attached glycosaminoglycan chains. They fill space in the ECM and resist compression.
Basal lamina
The ECM layer underlying epithelial cells, produced largely by fibroblasts.
Integrins
Dimeric transmembrane proteins that mediate adhesion and signalling between cells and the ECM.
Tight junctions
Seal the space between neighbouring cells so no molecules pass between them. Found in epithelial barriers (gut, kidney tubule).
Adherens junctions
Connect cells loosely, allowing flexibility and movement.
Desmosomes
Connect cells tightly and rigidly. Found in tissues under mechanical stress (skin, heart).
Gap junctions
Allow small molecules and ions to pass directly between neighbouring cells, enabling cell-to-cell communication.
Flux
The rate of diffusion in one direction. At equilibrium, flux continues in both directions but net flux is zero.
Net flux
The net gain of molecules on one side and net loss from the other. Zero at equilibrium.
Selective ion channels
Channels specific to one ion type (Na+, K+, or Cl-).
Nonselective ion channels
Channels that allow multiple monovalent cations (Na+, K+, Li+).
Constitutive channels
Ion channels that are always open.
Ca2+ ATPase pump
A primary active transporter that moves Ca2+ out of the cell (or into the ER/SR) using ATP hydrolysis.
Na+/K+ ATPase pump
A primary active transporter that pumps 3 Na+ out and 2 K+ in per ATP hydrolysed. Establishes the ion gradients essential for nerve impulses, osmotic balance, and secondary transport.
Glucose transport
A form of secondary active transport. The Na+/K+ pump creates a Na+ gradient; Na+ then flows back in through a symporter, dragging glucose with it.
Histone
A protein that binds DNA and regulates access for transcription. Histone modifications (acetylation, methylation) control gene expression.
RNase
An enzyme that degrades RNA, either from the end (exonuclease) or internally (endonuclease).
Ubiquitin
A small protein tag added to damaged or unneeded proteins, marking them for degradation by the proteasome.
Proteasome
A cytoplasmic complex that degrades ubiquitin-tagged proteins.
Alternative splicing
A process by which one gene can produce multiple mRNA variants (and therefore multiple proteins) by splicing different combinations of exons.
Allozymes
Allelic variants of an enzyme (different versions encoded by different alleles of the same gene).
Alleles
Different forms of the same protein encoded by the same gene but differing slightly in primary sequence.
Gene duplication
A mutation by which a genome acquires an additional copy of a gene, providing raw material for evolution.
Mobile elements
Regions of DNA that can be excised and inserted elsewhere in the genome (transposons).
ATP-binding cassette
A common structural motif found in diverse proteins that bind and hydrolyse ATP, including many membrane transporters.
The plasma membrane is a phospholipid bilayer with embedded proteins. Its fluid mosaic structure allows lateral movement of components.
Lipid rafts are thicker, more rigid patches enriched in cholesterol and sphingolipids. They concentrate signalling proteins.
Integral proteins span the membrane; peripheral proteins attach to one surface. Both contribute to transport, signalling, and structural roles.
Passive diffusion: small, non-polar molecules (O2, CO2, steroid hormones) cross without help. Rate depends on concentration gradient, membrane area, and lipid solubility.
Facilitated diffusion: polar or charged molecules use channels (fast, less selective) or carriers/permeases (slower, more selective). Still passive, still down the gradient.
Ion channels can be gated by ligands (ligand-gated), mechanical force (mechanogated), or voltage (voltage-gated, covered later). Constitutive channels remain open.
Active transport: moves substances against their gradient, always costs energy.
Primary: ATP hydrolysis directly powers the pump. The Na+/K+ ATPase (3 Na+ out, 2 K+ in per ATP) is the most important example, establishing the gradients that drive secondary transport and maintaining cell volume.
Secondary: uses the gradient created by primary transport. A symporter moves two substances in the same direction (Na+/glucose cotransport). An antiporter moves them in opposite directions.
Electrogenic transport changes the net charge across the membrane (Na+/K+ ATPase is electrogenic). Electroneutral transport does not.
Membrane potential is the voltage across the membrane, typically around -70 mV in a resting neuron (inside negative).
The Goldman equation predicts resting membrane potential from the permeabilities and concentrations of Na+, K+, and Cl-.
Equilibrium potential (for a single ion) and reversal potential (for a channel carrying multiple ions) describe the voltage at which net ion flow is zero.
Excitable cells (neurons, muscle) rapidly change their membrane potential in response to stimuli, producing action potentials.
Microfilaments (actin): thin, flexible, drive cell shape changes and muscle contraction.
Microtubules (tubulin): rigid, hollow tubes that serve as tracks for motor proteins and form the mitotic spindle.
Intermediate filaments (keratin, vimentin, etc.): rope-like, provide mechanical strength, no motor proteins associated.
Motor proteins: kinesin moves toward the plus end of microtubules (outward); dynein moves toward the minus end (inward). Myosin works along actin filaments.
The ER processes and folds proteins (rough ER) and synthesises lipids (smooth ER).
Vesicles bud from the ER and Golgi, coated in clathrin, and deliver cargo to the membrane or extracellular space.
Exocytosis: vesicle fuses with the membrane and releases contents outside. Endocytosis: membrane engulfs material and brings it inside.
Pinocytosis (fluids) and phagocytosis (large particles) are types of endocytosis.
The ECM is the structural scaffold outside cells. Its main components are collagen (strength), proteoglycans (compression resistance), and the basal lamina (epithelial support).
Integrins connect the ECM to the cytoskeleton and transmit signals in both directions.
Cell junctions:
Tight junctions: seal gaps, create barriers (gut epithelium).
Adherens junctions: flexible connections.
Desmosomes: rigid connections, resist tension (skin, heart).
Gap junctions: allow direct communication between cells.
Histones control DNA accessibility for transcription. Modifications (acetylation, methylation) loosen or tighten histone binding.
Alternative splicing allows one gene to produce multiple protein variants by combining different exons.
Ubiquitin tags damaged proteins for degradation by the proteasome. This system is essential for protein quality control.
RNases degrade RNA, controlling mRNA lifespan and gene expression at the post-transcriptional level.
The Na+/K+ ATPase consumes roughly 20-30% of the body's resting energy expenditure. Drugs that inhibit it (cardiac glycosides like digoxin) are used to treat heart failure by increasing intracellular Ca2+ and strengthening contractions.
Cystic fibrosis results from a defective Cl- channel (CFTR), illustrating how a single ion channel defect can cause systemic disease.
Students think facilitated diffusion requires energy because a protein is involved. It does not. The protein provides a pathway; the driving force is still the electrochemical gradient.
Students confuse channels and carriers. Channels form open pores and are fast. Carriers bind substrates and change conformation, making them slower but more selective.
Students assume "active transport" always means "uses ATP." Primary active transport does. Secondary active transport uses a pre-existing ion gradient, not ATP directly.
Students forget that the Na+/K+ ATPase is electrogenic. Because it moves 3 positive charges out for every 2 it brings in, it contributes a small amount to the resting membrane potential.
⚠️ Be able to classify any transport example as passive diffusion, facilitated diffusion, primary active, or secondary active.
⚠️ Know the stoichiometry of the Na+/K+ ATPase (3 Na+ out, 2 K+ in) and why it is electrogenic.
⚠️ Understand the relationship between the Na+/K+ pump and secondary glucose transport.
⚠️ Be able to name the four types of cell junctions and state the function of each.
⚠️ Know the three cytoskeletal filament types, their protein subunits, and associated motor proteins.
True or False: Facilitated diffusion requires ATP. (False. It uses a protein but is still driven by the electrochemical gradient.)
Fill in the blank: The Na+/K+ ATPase pumps ______ Na+ out and ______ K+ in per ATP hydrolysed. (3; 2)
True or False: Kinesin moves cargo toward the minus end of microtubules. (False. Kinesin moves toward the plus end. Dynein moves toward the minus end.)
Fill in the blank: ______ junctions seal the space between cells, while ______ junctions allow direct cell-to-cell communication. (Tight; gap)
True or False: The proteasome degrades proteins tagged with ubiquitin. (True.)
Q: A cell is treated with ouabain, which inhibits the Na+/K+ ATPase. Predict the consequences for intracellular Na+ concentration, cell volume, and secondary glucose transport.
A: Intracellular Na+ rises because it is no longer being pumped out. The Na+ gradient that normally drives secondary glucose transport collapses, so glucose uptake falls. The rising intracellular Na+ also draws water in by osmosis, causing the cell to swell.
Q: Explain why the Goldman equation, rather than the Nernst equation, is used to predict the resting membrane potential.
A: The Nernst equation calculates the equilibrium potential for a single ion. The resting membrane potential depends on the combined contributions of multiple ions (Na+, K+, Cl-), weighted by their relative permeabilities. The Goldman equation accounts for all of these simultaneously.
Q: A tissue has abundant desmosomes. What can you infer about the mechanical demands on that tissue?
A: Desmosomes connect cells in a tight, rigid manner suited for resisting mechanical stress. Tissues rich in desmosomes (skin, cardiac muscle) experience frequent stretching, compression, or shear forces.
Q: How does alternative splicing increase protein diversity without increasing the number of genes?
A: By combining different exons from the same pre-mRNA transcript, a single gene can produce multiple mRNA variants, each encoding a slightly different protein. This allows one gene to serve multiple functions in different tissues or developmental stages.
Transport mechanisms connect back to electrochemical gradients (Doc 2) and forward to neurophysiology and muscle contraction.
The Na+/K+ ATPase ties energy expenditure (Doc 3, oxidative phosphorylation) to ion homeostasis and nerve function.
Cell junctions and the ECM connect to tissue-level organisation and organ physiology covered later in the course.
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