The Sliding Filament Theory

Figure 2
Figure Detail
In 1954, scientists published two groundbreaking papers describing the molecular basis of muscle contraction. These
papers described the position of myosin and actin filaments at various stages of contraction in muscle fibers and proposed
how this interaction produced contractile force. Using high-resolution microscopy, A. F. Huxley and R. Niedergerke (1954)
and H. E. Huxley and J. Hanson (1954) observed changes in the sarcomeres as muscle tissue shortened. They observed
that one zone of the repeated sarcomere arrangement, the "A band," remained relatively constant in length during
contraction (Figure 2A). The A band contains thick filaments of myosin, which suggested that the myosin filaments remained
central and constant in length while other regions of the sarcomere shortened. The investigators noted that the "I band," rich
in thinner filaments made of actin, changed its length along with the sarcomere. These observations led them to propose the
sliding filament theory, which states that the sliding of actin past myosin generates muscle tension. Because actin is tethered
to structures located at the lateral ends of each sarcomere called z discs or "z bands," any shortening of the actin filament
length would result in a shortening of the sarcomere and thus the muscle. This theory has remained impressively intact
(Figure 2B).

An Analogy for Sliding Filaments in a Sarcomere Shortening Event

Imagine that you are standing between two large bookcases loaded with books. These large bookcases are several meters
apart and are positioned on rails so that they can be easily moved. You are given the task of bringing the two bookcases
together, but you are limited to using only your arms and two ropes. Standing centered between the bookcases, you pull on
the two ropes one per arm which are tied securely to each bookcase. In a repetitive fashion, you pull each rope toward
you, regrasp it, and then pull again. Eventually, as you progress through the length of rope, the bookcases move together
and approach you. In this example, your arms are similar to the myosin molecules, the ropes are the actin filaments, and the
bookcases are the z discs to which the actin is secured, which make up the lateral ends of a sarcomere. Similar to the way
you would remain centered between the bookcases, the myosin filaments remain centered during normal muscle contraction
(Figure 2B).

What Are Cross Bridges, and How Do They Relate to Sliding Filaments?
One important refinement of the sliding filament theory involved the particular way in which myosin is able to pull upon actin
to shorten the sarcomere. Scientists have demonstrated that the globular end of each myosin protein that is nearest actin,

called the S1 region, has multiple hinged segments, which can bend and facilitate contraction (Hynes et al. 1987; Spudich
2001). The bending of the myosin S1 region helps explain the way that myosin moves or "walks" along actin. The slimmer
and typically longer "tail" region of myosin (S2) also exhibits flexibility, and it rotates in concert with the S1 contraction
(Figure 3A).
The movements of myosin appear to be a kind of molecular dance. The myosin reaches forward, binds to actin, contracts,
releases actin, and then reaches forward again to bind actin in a new cycle. This process is known as myosin-actin cycling.
As the myosin S1 segment binds and releases actin, it forms what are called cross bridges, which extend from the thick
myosin filaments to the thin actin filaments. The contraction of myosin's S1 region is called the power stroke (Figure 3). The
power stroke requires the hydrolysis of ATP, which breaks a high-energy phosphate bond to release energy.

Figure 3: The power stroke of the swinging cross-bridge model, via myosin-actin cycling
Actin (red) interacts with myosin, shown in globular form (pink) and a filament form (black line). The model shown is that of
H. E. Huxley, modified to indicate bending (curved arrow) near the middle of the elongated cross bridge (subfragment 1, or
S1) which provides the working stroke. This bending propels actin to the right approximately 10 nanometers (10 nm step).
S2 tethers globular myosin to the thick filament (horizontal yellow line), which stays in place while the actin filament moves.
Modified from Spudich (2001).
2001 Nature Publishing Group Spudich, J. A. The myosin swinging cross-bridge model. Nature Reviews
Molecular Cell Biology 2, 387-392 (2001). All rights reserved.
Figure Detail
Specifically, this ATP hydrolysis provides the energy for myosin to go through this cycling: to release actin, change
its conformation, contract, and repeat the process again (Figure 4). Myosin would remain bound to actin indefinitely
causing the stiffness of rigor mortis if new ATP molecules were not available (Lorand 1953).
Two key aspects of myosin-actin cycling use the energy made available by the hydrolysis of ATP. First, the action of the
reaching myosin S1 head uses the energy released after the ATP molecule is broken into ADP and phosphate. Myosin
binds actin in this extended conformation. Second, the release of the phosphate empowers the contraction of the myosin S1
region (Figure 4).

Figure 4: Illustration of the cycle of changes in myosin shape during cross-bridge cycling (1, 2, 3, and 4)
ATP hydrolysis releases the energy required for myosin to do its job. AF: actin filament; MF myosin filament. Modified from
Goody (2003).
2003 Nature Publishing Group Goody, R. S. The missing link in the muscle cross-bridge cycle. Nature Structural
Biology 10, 773-775 (2003). All rights reserved.
Figure Detail

What Regulates Sarcomere Shortening?

Figure 5

Calcium and ATP are cofactors (nonprotein components of enzymes) required for the contraction of muscle cells. ATP
supplies the energy, as described above, but what does calcium do? Calcium is required by two proteins, troponin and
tropomyosin, that regulate muscle contraction by blocking the binding of myosin to filamentous actin. In a resting sarcomere,
tropomyosin blocks the binding of myosin to actin. In the above analogy of pulling shelves, tropomyosin would get in the way
of your hand as it tried to hold the actin rope. For myosin to bind actin, tropomyosin must rotate around the actin filaments to
expose the myosin-binding sites. In 1994, William Lehman and his colleagues demonstrated how tropomyosin rotates by
studying the shape of actin and myosin in either calcium-rich solutions or solutions containing low calcium (Lehman, Craig, &
Vibertt 1994). By comparing the action of troponin and tropomyosin under these two conditions, they found that the

presence of calcium is essential for the contraction mechanism. Specifically, troponin (the smaller protein) shifts the position
of tropomyosin and moves it away from the myosin-binding sites on actin, effectively unblocking the binding site (Figure 5).
Once the myosin-binding sites are exposed, and if sufficient ATP is present, myosin binds to actin to begin cross-bridge
cycling. Then the sarcomere shortens and the muscle contracts. In the absence of calcium, this binding does not occur, so
the presence of free calcium is an important regulator of muscle contraction.

Unresolved Questions
Is muscle contraction completely understood? Scientists are still curious about several proteins that clearly influence muscle
contraction, and these proteins are interesting because they are well conserved across animal species. For example,
molecules such as titin, an unusually long and "springy" protein spanning sarcomeres in vertebrates, appears to bind to
actin, but it is not well understood. In addition, scientists have made many observations of muscle cells that behave in ways
that do not match our current understanding of them. For example, some muscles in mollusks and arthropods generate
force for long periods, a poorly understood phenomenon sometimes called "catch-tension" or force hysteresis (Hoyle 1969).
Studying these and other examples of muscle changes (plasticity) are exciting avenues for biologists to explore. Ultimately,
this research can help us better understand and treat neuromuscular systems and better understand the diversity of this
mechanism in our natural world.

Summary
Muscle contraction provides animals with great flexibility, allowing them to move in exquisite ways. The molecular changes
that result in muscle contraction have been conserved across evolution in the majority of animals. By studying sarcomeres,
the basic unit controlling changes in muscle length, scientists proposed the sliding filament theory to explain the molecular
mechanisms behind muscle contraction. Within the sarcomere, myosin slides along actin to contract the muscle fiber in a
process that requires ATP. Scientists have also identified many of the molecules involved in regulating muscle contractions
and motor behaviors, including calcium, troponin, and tropomyosin. This research helped us learn how muscles can change
their shapes to produce movements.

Describe the Sliding Filament Theory of

muscle contraction.
The Sliding Filament Theory is a description of the process of muscular contraction. Muscles contract
in order to move limbs or maintain a certain position or posture. However, for the muscle as a whole
to contract, the actin and myosin filaments must overlap, causing the sarcomere to shorten. This
process is triggered by the release of calcium ions in the presence of the proteins troponin and
tropomyosin. The release of calcium, which is provided by the energy source adenosine triphosphate
(ATP), facilitates the interaction of myosin and actin at the molecular level. At high levels of
magnification it is detected those small bridges, known as myosin cross-bridges, on the thick filaments
extend over to the thin filaments. These cross-bridges continually attach, rotate, detach, and reattach
which results in the sliding of the filaments, shortening of the sarcomere, and finally what we see to
be muscle contraction.