Difficulty: Intermediate | Prerequisites: Part 1 of these notes (cytoskeleton and motor proteins), basic understanding of ATP hydrolysis.
This section bridges the general cytoskeleton material from Part 1 into how muscles actually work. Most actin-based movement in the body uses the motor protein myosin, and muscle cells have evolved a highly specialised arrangement of actin and myosin (the sarcomere) to produce powerful, coordinated contractions. Understanding sarcomere structure is essential because it explains why muscles shorten, which bands change during contraction, and why the absence of ATP causes rigor mortis. You should be comfortable with microfilaments, actin polymerisation, and the concept of motor proteins pulling on filaments before starting here.
Myosin is an ATPase motor protein that pulls on actin filaments through a repeating cross-bridge cycle of grasp, pull, and release. In muscle cells, hundreds of myosin molecules are bundled into thick filaments, which interleave with actin-based thin filaments inside repeating units called sarcomeres. When the sarcomere shortens, the muscle contracts.
Myosin
A motor protein (ATPase) that walks along actin filaments, converting chemical energy from ATP into mechanical force. Think of it as the arm that pulls on the actin rope.
Cross-bridge cycle
The repeating sequence of myosin binding to actin (cross-bridge formation), bending (power stroke), releasing, and re-extending. This is the fundamental engine of muscle contraction.
Power stroke
The structural change in which the myosin head bends, pulling the actin filament. In simple terms, this is the "pull" part of the grasp-pull-release cycle.
Rigor mortis
The stiffening of muscles after death caused by the absence of ATP. Without ATP, myosin heads cannot release from actin, locking the muscle in a contracted state.
Duty cycle
The proportion of the cross-bridge cycle time during which myosin is attached to actin. For most myosins it is about 0.5; for muscle-specific Myosin II it is only 0.05, allowing many heads to take turns pulling the same filament.
Unitary displacement
The distance a myosin head moves the actin filament in a single power stroke. In muscle (Myosin II), this is short (5 to 15 nm), because force matters more than distance.
Sarcomere
The basic contractile unit of striated muscle, defined as the region between two Z-disks. Think of it as one repeating "tile" in the muscle's structure.
Myocyte
A muscle cell. Myocytes are contractile cells unique to animals.
Thick filament
A polymer of roughly 300 Myosin II hexamers bundled together in the sarcomere. The thick filament provides the pulling force during contraction.
Thin filament
A polymer of alpha-actin (in muscle cells), stabilised at its ends by CapZ and tropomodulin, with troponin and tropomyosin on its surface to regulate contraction.
Z-disk (Z-line)
The boundary structure of a sarcomere. Thin filaments are anchored to the Z-disk by CapZ proteins and extend inward toward the centre.
A-band
The anisotropic band: the middle region of the sarcomere occupied by thick filaments. Its width does not change during contraction.
I-band
The isotropic band: the region on either side of the Z-disk occupied by thin filaments only. It narrows during contraction.
H-zone
The central region of the A-band where only thick filament tails are present (no thin filaments overlap). It disappears when the muscle is fully contracted.
Titin
A giant elastic protein that anchors each thick filament to the Z-disk, keeping it centred in the sarcomere. Titin is the only sarcomeric protein that can be compressed.
Nebulin
A protein that runs along the length of the thin filament, helping to regulate its length.
Troponin
A regulatory protein complex on the thin filament that includes TnC (calcium-binding subunit), TnI (inhibitory subunit), and TnT (tropomyosin-binding subunit). When calcium binds to TnC, troponin shifts tropomyosin to expose the myosin-binding site on actin.
Tropomyosin
A regulatory protein that wraps around the actin filament and blocks the myosin-binding sites at rest. In simple terms, tropomyosin is the guard that keeps myosin away from actin until calcium arrives.
Myofibril
A long chain of sarcomeres connected end to end, extending the full length of a muscle cell. More myofibrils arranged in parallel = more contractile force.
Most actin-based movements involve myosin. There are 17 classes of myosin with multiple isoforms in each class, but all share the same basic three-part structure:
Head -- contains the ATPase active site and the actin-binding site
Neck -- contains regulatory and essential light chains; hormones regulate myosin function by phosphorylating these light chains
Tail -- binds to cargo or to other myosin molecules (in thick filaments)
The sliding filament model is the core mechanism of actin-myosin force generation. It works like pulling yourself along a rope:
Actin = the rope
Myosin = your arm
The cycle: grasp the rope, pull (power stroke), release, extend forward, grasp again
Each cycle involves two processes:
A chemical reaction: myosin binds to actin, forming a cross-bridge
A structural change: the myosin head bends, pulling the actin (power stroke)
The full cross-bridge cycle: cross-bridge formation, power stroke, release, extension. ATP is required to release myosin from actin and reset the head. Without ATP, myosin stays locked to actin, which is why the absence of ATP after death causes rigor mortis.
The direction of movement depends on which component is anchored. If myosin is anchored, actin moves. If actin is anchored, myosin moves. This is sometimes called the tug-of-war model: the structural arrangement of actin and myosin, specifically which of the two is free to move, determines the outcome.
Two factors govern how effectively myosin generates movement:
This is the distance myosin moves actin in a single power stroke. It depends on:
Myosin neck length (longer neck = longer step)
Location of binding sites on actin
Helical structure of actin, which allows 3D movement
In muscle (Myosin II), unitary displacement is short, only 5 to 15 nm. This is because muscle is optimised for force, not distance.
Duty cycle = cross-bridge time / total cross-bridge cycle time. It is the fraction of time myosin spends attached to actin.
Typical myosin: duty cycle of about 0.5
Muscle-specific Myosin II: duty cycle of only 0.05
A low duty cycle means each myosin head is attached for a very short time, which is an advantage in muscle: it means one head does not block others from pulling. Multiple myosin dimers work in teams, with one monomer pulling while others are detaching and resetting. More dimers working together = a smaller duty cycle per head is acceptable.
Muscle cells (myocytes) are contractile cells unique to animals. There are three types: skeletal (voluntary movement), cardiac (heart), and smooth (blood vessels, digestive tract).
Polymers of myosin, roughly 300 Myosin II hexamers per thick filament
150 hexamers oriented end to end in each direction, giving 300 myosin heads and 600 necks per filament
Many myosin heads working together generate large forces
Polymers of alpha-actin (beta-actin in non-muscle cells)
Stabilised at the (+) end by CapZ and at the (-) end by tropomodulin
Troponin and tropomyosin sit on the outer surface and regulate access to the myosin-binding site
Muscle cells fall into two structural categories based on how actin and myosin are arranged:
Striated muscle (skeletal and cardiac): actin and myosin are arranged in parallel, in repeating sarcomere units, giving a striped appearance under the microscope. The parallel arrangement allows simultaneous stimulation and large force generation.
Smooth muscle: actin and myosin are scattered throughout the cell with no regular pattern. No sarcomeres, no striations. Found mainly in blood vessel walls, the digestive tract, airways, and the kidney.
The sarcomere is the basic contractile unit of striated muscle, running from one Z-disk to the next.
Z-disk: the border of each sarcomere. Thin filaments attach here via CapZ proteins and extend inward toward the centre.
A-band: the middle region, occupied by thick filaments. Contains lots of protein.
I-band: the region on either side of the Z-disk, occupied only by thin filaments.
H-zone (middle line): the central strip of the A-band where only thick filament tails are present, with no thin filament overlap.
Tropomodulin caps the (-) end of thin filaments to prevent disassembly.
Titin connects thick filaments to the Z-disk, keeping them centred. Titin is the only sarcomeric protein that can be compressed.
Nebulin runs along the length of the thin filament.
In 3D, each thick filament is surrounded by six thin filaments, and each thin filament is associated with three thick filaments. The ratio of thick to thin filaments is 1:2.
At rest, thick and thin filaments do not overlap in the H-zone. The I-band and H-zone are at maximum width.
Upon stimulation, the cross-bridge cycle begins and thin filaments are pulled inward toward the centre of each thick filament:
The two thin filaments from opposite Z-disks slide toward each other
The H-zone narrows and eventually disappears
The I-band becomes very narrow
The A-band width remains unchanged (the thick filaments do not change length)
Z-disks move closer together, compressing titin
Neither thick nor thin filaments shorten; they slide past each other
In a fully contracted muscle, the ends of the actin filaments from opposite sides overlap in the centre.
Sarcomeres are connected end to end into long chains called myofibrils, which extend the full length of the muscle cell.
Myofibrils are arranged in parallel within the cell
More myofibrils = more contractile force
Muscle cells can be very large (up to 60 cm) because they fuse with each other during development, so a single muscle cell can contain many nuclei
In neurons, excitation leads to neurotransmitter release; in muscles, excitation leads to contraction
Rigor mortis is a direct consequence of the cross-bridge cycle: when ATP runs out after death, myosin heads remain locked to actin and muscles stiffen. Understanding this mechanism is important in forensic science for estimating time of death. The Myosin II duty cycle of 0.05 also explains why muscle can sustain powerful contractions: hundreds of myosin heads take turns, so the filament is always being pulled even though each individual head is attached only briefly.
Students often think the thick and thin filaments themselves shorten during contraction. They do not. The filaments slide past each other; neither changes length.
Students often believe the A-band gets narrower during contraction. The A-band stays the same width because it is defined by the thick filaments, which do not shorten. It is the I-band and H-zone that narrow.
Students sometimes confuse "no ATP = relaxation." The opposite is true: ATP is required for myosin to release actin. No ATP = permanent contraction (rigor mortis).
Students sometimes think a higher duty cycle means more force. In muscle, a low duty cycle (0.05) is advantageous because each head gets out of the way quickly, allowing hundreds of heads to take turns.
⚠️ Be able to describe the cross-bridge cycle in order: binding, power stroke, release, extension.
⚠️ Know that ATP is needed for release (not for the power stroke itself). No ATP = rigor mortis.
⚠️ Know what happens to each sarcomere region during contraction: I-band narrows, H-zone disappears, A-band unchanged.
⚠️ Be able to explain why muscle uses Myosin II with a very low duty cycle (0.05).
⚠️ Understand the difference between striated and smooth muscle at the structural level.
⚠️ Know the ratio of thick to thin filaments in the sarcomere (1:2) and that each thick filament is surrounded by six thin filaments.
True or false: ATP is needed for the power stroke. (False. ATP is needed for myosin to release from actin and reset.)
Fill in the blank: The A-band width ______ during contraction. (Remains unchanged.)
True or false: Each thick filament is surrounded by three thin filaments. (False. Six thin filaments surround each thick filament.)
Fill in the blank: The duty cycle of muscle Myosin II is approximately ______. (0.05.)
True or false: Smooth muscle contains sarcomeres. (False. Smooth muscle has no sarcomeres.)
Q: Describe the four steps of the cross-bridge cycle.
A: (1) Myosin head binds to actin, forming a cross-bridge. (2) Myosin head bends (power stroke), pulling the actin filament. (3) ATP binds to myosin, causing it to release from actin. (4) ATP hydrolysis resets the myosin head to its extended position, ready to bind again.
Q: Why does the A-band remain the same width during contraction while the I-band narrows?
A: The A-band is defined by the thick filaments, which do not change length. The I-band contains only thin filaments; as contraction pulls the thin filaments inward, the region of thin-filament-only space shrinks.
Q: Explain why the absence of ATP leads to rigor mortis rather than relaxation.
A: ATP is required for myosin to detach from actin. Without ATP, the cross-bridges remain locked in the bound state, making the muscle permanently stiff.
Q: What is the advantage of Myosin II having a very low duty cycle (0.05) in muscle?
A: A low duty cycle means each myosin head is attached to actin for a very brief period, so it does not block other myosin heads from pulling. Hundreds of heads can take turns, maintaining continuous force on the thin filament.
Q: Name the proteins that cap each end of the thin filament in a sarcomere and explain why capping is important.
A: CapZ caps the (+) end at the Z-disk, and tropomodulin caps the (-) end. Capping prevents treadmilling and maintains a stable filament length, which is essential for the repeating sarcomere structure that generates coordinated force.
This material builds directly on Part 1 (cytoskeleton and motor proteins) and feeds into Part 3 (excitation-contraction coupling and calcium signalling). The troponin-tropomyosin regulatory system introduced here is the bridge to understanding how calcium triggers contraction. The structural differences between striated and smooth muscle introduced here will matter when you study the cardiovascular and digestive systems later in the course.
myosin, myosin II, ATPase, cross-bridge cycle, power stroke, sliding filament model, rigor mortis, duty cycle, unitary displacement, sarcomere, myocyte, muscle cell, thick filament, thin filament, alpha-actin, Z-disk, Z-line, A-band, I-band, H-zone, titin, nebulin, CapZ, tropomodulin, troponin, TnC, TnI, TnT, tropomyosin, myofibril, striated muscle, skeletal muscle, cardiac muscle, smooth muscle, regulatory light chain, essential light chain, actin-myosin interaction, tug-of-war model, muscle contraction