Length dependence of active force production in skeletal

muscle
D. E. Rassier, B. R. MacIntosh and W. Herzog
Journal of Applied Physiology 86:1445-1457, 1999.

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 invited review
Length dependence of active force production
in skeletal muscle
D. E. RASSIER, B. R. MACINTOSH, AND W. HERZOG
Human Performance Laboratory, Faculty of Kinesiology,
The University of Calgary, Calgary, Alberta, Canada T2N 1N4

Rassier, D. E., B. R. MacIntosh, and W. Herzog. Length depen-

dence of active force production in skeletal muscle. J. Appl. Physiol. 86(5):
1445–1457, 1999.—The sliding filament and cross-bridge theories of
muscle contraction provide discrete predictions of the tetanic force-length
relationship of skeletal muscle that have been tested experimentally. The
active force generated by a maximally activated single fiber (with
sarcomere length control) is maximal when the filament overlap is
optimized and is proportionally decreased when overlap is diminished.

Downloaded from jap.physiology.org on April 4, 2005

The force-length relationship is a static property of skeletal muscle and,
therefore, it does not predict the consequences of dynamic contractions.
Changes in sarcomere length during muscle contraction result in modula-
tion of the active force that is not necessarily predicted by the cross-
bridge theory. The results of in vivo studies of the force-length relation-
ship suggest that muscles that operate on the ascending limb of the
force-length relationship typically function in stretch-shortening cycle
contractions, and muscles that operate on the descending limb typically
function in shorten-stretch cycle contractions. The joint moments pro-
duced by a muscle depend on the moment arm and the sarcomere length
of the muscle. Moment arm magnitude also affects the excursion (length
change) of a muscle for a given change in joint angle, and the number of
sarcomeres arranged in series within a muscle fiber determines the
sarcomere length change associated with a given excursion.
force-length relationship; sarcomere length; isometric contraction; slid-
ing filament theory; cross-bridge theory; moment-angle relationship;
force-calcium relationship

THE FACT THAT PASSIVE FORCE, peak single-twitch force,
and peak tetanic isometric force depend on muscle
length has been well described over 100 years ago by
Blix in a series of three scientific papers (6–8). Blix
performed experiments on frog striated muscles and
found for the adductors of the thigh and the gastrocne-
mius that isometric force increased with increasing
lengths, reached a plateau, and then decreased. Based
on these correct observations and the available struc-
tural information, Blix (8) proposed a mechanism of
force production and shortening that was based on the
shortening of longitudinally arranged ‘‘protein fila-
ments’’ (Protoplasmastäbchen or Inotagmen).
The length dependence of skeletal muscle force pro-
duction may be conveniently divided into two broad
categories: maximal and submaximal contractions. For
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maximal contractions, the length dependence of force is
typically referred to as the force-length relationship.
Force-length relationships are obtained during isomet-
ric contractions; i.e., either the total muscle length, the
fiber length, or the sarcomere length (depending on the
preparation) is kept constant during the experiment.
With few exceptions (28), the force values in force-
length experiments are the maximal steady-state forces
that are reached during isometric contractions. Sub-
maximal contractions are all contractions for which
maximal activation is not achieved. For submaximal
contractions, we will not use the term ‘‘force-length
relationship’’ but will talk about the length dependence
of force production.
This review is divided into four parts. In the first
part, the theoretical background for the force-length
relationship is given based on the cross-bridge theory.
In the second and third parts, the force-length relation-
ship and the length dependence of force production are
discussed for single-fiber and for entire muscle prepara-
tions, respectively. In the fourth part, some functional
1445
1446 INVITED REVIEW

implications of the force-length property for in vivo

force and moment production are described.
Throughout the review, length dependence of force
production refers to active force production, except
when specifically indicated. Active force is defined as
the rise in force observed on activation of a muscle and
is associated with cross-bridge interactions between
myosin and actin. This restriction to active force produc-
tion should not be interpreted as a value judgment on
the importance of active vs. passive muscular forces. It
merely reflects the interest of the authors in active
rather than passive muscle properties.
PART 1: THEORETICAL BACKGROUND OF THE
FORCE-LENGTH RELATIONSHIP

The force-length relationship of sarcomeres may be

explained, to a large degree, by the sliding filament (41,
44) and the cross-bridge theories (40, 43). The sliding
filament theory assumes that length changes in sarco-
meres, fibers, and muscles are accomplished by relative
sliding of the essentially inextensible myofilaments,

Downloaded from jap.physiology.org on April 4, 2005

actin and myosin, within a sarcomere (Fig. 1). [Recent
evidence suggests that actin and, possibly, the myosin
filaments are not as inextensible as originally assumed
(27, 37, 46, 52, 84); however, myofilament compliance
may safely be ignored in the following considerations].
The cross-bridge theory suggests that the relative
sliding of actin and myosin is caused by independent
force generators; i.e., the cross bridges. Of particular
importance for the derivation of the sarcomere force-
length relationship are the following assumptions un-
derlying the cross-bridge theory.
1) The cross bridges are uniformly distributed along
the length of the myosin filament.
2) The actin filament has uniformly distributed
attachment sites for the cross bridges.
3) The attachment/detachment probability of a cross
bridge only depends on its location relative to an actin
attachment site and is independent of its prior history
or its neighboring cross bridges (40).
4) Each cross bridge exerts, on average, the same
amount of force as any other cross bridge.
Cross bridges are small and have a limited attach-
ment range. Therefore, cross-bridge attachments only
occur in the actin-myosin overlap zone of a sarcomere
(Fig. 1). Together with the assumptions underlying the
cross-bridge theory, this limitation implies that the
Fig. 1. Schematic representation of a sarcomere.
Fig. 2. Force-length relationship of frog skeletal muscle sarcomere,
as derived first by Gordon et al. (28) (top), and schematic sarcomeres
corresponding to crucial points (1–5) labeled on the force-length
curve (bottom).
maximal isometric force of a sarcomere is linearly
related to the amount of actin-myosin overlap (Fig. 2).
In frog striated muscle, actin and myosin lengths are
⬃0.95 and 1.6 µm, respectively; the Z-line width (Figs.
1 and 2) is ⬃0.1 µm, and the central part of the myosin
filament (⬃0.2 µm) does not contain cross bridges (45,
85). With these geometrical assumptions, it is obvious
that maximal overlap between actin and myosin occurs
at a sarcomere length of ⬃2.0 µm [i.e., twice the actin
length (1.9 µm) plus the Z-line width (0.1 µm)]; there-
fore, sarcomere force should be maximal at a sarcomere
length of 2.0 µm. A reduction in actin-myosin overlap
caused by extension of the sarcomere by 0.2 µm does
not decrease the force potential, because the midzone of
the myosin filament does not contain cross bridges.
Extending the sarcomere beyond 2.2 µm is associated
with a linear decrease in the number of potential
actin-myosin interactions, and active force production
should become zero at a sarcomere length of ⬃3.6 µm
(Fig. 2) [twice the thin filament length (1.9 µm) ⫹ the
thick filament length (1.6 µm) ⫹ the width of the Z line
(0.1 µm)], where no overlap of the myofilaments occurs.
The cross-bridge theory predicts well the results of
the experimental sarcomere force-length relationship
for the plateau region (2.0–2.2 µm) and the descending
 INVITED REVIEW
limb (2.2–3.6 µm). On the ascending limb of the force-
length relationship (i.e., sarcomere lengths ⬍2.0 µm),
active isometric sarcomere force decreases with decreas-
ing length (Fig. 2). There are two conceptual possibili-
ties why force decreases in this region of the force-
length relationship: 1) active force production may be
reduced and/or 2) internal forces may oppose the active
forces. Active force production may be reduced because
of an increasing lateral distance between the actin and
myosin filaments at short length effecting reduced
probability of cross-bridge interaction (26). Interfer-
ence of cross-bridge interaction may occur with double
overlap of the thin filaments (28). Also, below sarco-
mere length of 1.7 µm, proper cross-bridge attachments
may be limited by deformation of the myosin filament.
Internal forces that may oppose active forces include
forces associated with deforming actin and myosin
filaments. Particularly myosin deformation, which oc-
curs when the Z lines of the sarcomere push against the
ends of the myosin filament at a sarcomere length of
⬃1.7 µm, appears to cause a decrease in force (28) (Fig.
2). Furthermore, when frog sarcomeres are shortened
below optimal length and are not constrained, they
tend to extend to ⬃2.1 µm (72). The magnitude of this
restoring force is not known, but it presumably would
subtract from the active force. It has been suggested
that the restoring force is minimal in the sarcomere
length range from 1.65 to 2.0 µm, since maximal velocity of
fiber shortening is not affected (48). Last, fluid and osmotic
pressures may be elevated in shortened muscle fibers
and may contribute to oppose the active sarcomere
forces, as suggested by Sato (77) and Gordon et al. (28).
The above theoretical relationship between sarco-
mere length and force was derived for myofilament
lengths found in frog striated muscles. Actin filament
lengths vary appreciably across species (33, 85), and
this variation should influence the shape of the sarco-
mere force-length relationship. For example, the theo-
retical plateau region and descending limb of cat and
human skeletal muscles are shifted to the right of that
for frog (Fig. 3). The shift corresponds to twice the
difference in actin filament lengths between the spe-
cies. Human and frog actin filament lengths are ⬃1.27
and 0.95 µm, respectively; therefore, the shift in the
Fig. 3. Sarcomere force-length relationship in frog, cat, and human
skeletal muscles.
1447
Fig. 4. Actual data points of a sarcomere force-length relationship
obtained around the plateau region of frog skeletal muscle. Error
bars indicate ⫾1 SE. [Adapted from Gordon et al. (28).]
theoretical plateau and descending limb region for
human and frog muscles is ⬃2 ⫻ (1.27 ⫺ 0.95) ⫽ 0.64
µm. The ascending limb region for human and cat
sarcomeres has not been determined and cannot be
Downloaded from jap.physiology.org on April 4, 2005
derived without further assumptions. Sarcomere force-
length relationships of mammalian skeletal muscle are
rare; however, an excellent relationship was derived
experimentally by ter Keurs et al. (83) for the rat
extensor digitorum muscle.
The force-length property of muscle is a static prop-
erty; static in the sense that one experimental trial
gives one data point. This basic fact is often neglected
in theoretical models of muscle, presumably because
the force-length relationship is typically represented
with continuous lines (e.g., Fig. 2) rather than by
isolated data points (Fig. 4) (Fig. 2; Ref. 28), and
mathematical descriptions of the force-length relation-
ship are given as continuous functions (89), implying
that the relationship is continuous in time and length.
However, this implication is not correct.
Considering the force-length relationship as a con-
tinuous, dynamic property has led to the notion of
instability in sarcomere length on the descending limb
of the force-length curve. The negative slope of the
descending limb represents the behavior of a softening
material, an unstable behavior. However, the notion of
instability may be incorrect, because a fiber that short-
ens or elongates shows a positive stiffness. For ex-
ample, Edman et al. (14) showed that a fiber that is
stretched on the descending limb of the force-length
relationship will become stronger as it is stretched,
rather than weaker, as one should expect based on the
force-length relationship (Fig. 5). However, and even
more importantly, Edman et al. (14, 15) showed that
the force enhancement observed during the stretch did
not disappear, but some of the force enhancement was
maintained for a long time (4.2 s). This additional force
following the stretch did not only cause a force enhance-
ment relative to the isometric force at the stretched
length but also produced an isometric, steady-state
force following the stretch that was larger than the
isometric force preceding the stretch. This latter result,
if transferable to the sarcomere level, would ensure
unconditional stability of sarcomere length on the
1448 INVITED REVIEW
Fig. 5. Actual data of force enhancement and positive sarcomere
stiffness on descending limb of the force-length relationship for frog
skeletal muscle. Relationship between force (stress) and sarcomere
length; r and the corresponding solid lines represent isometric
force-length relationship for single fibers from semitendinosus of
Rana temporaria. A: j and the corresponding line represent steady-
state force at 4.3 s after completion of 0.2 µm/sarcomere stretches at
constant speed. Dashed lines connecting the isometric force-length
curve with steady-state force values following stretch show the origin
and the end of stretch. Note that dashed lines do not show the actual
force-length trace followed during stretch. B: stretches of varying
lengths (different symbols), beginning at 2 different initial lengths
are illustrated. Temperature: 1.49°C, cross-sectional area of fiber:
10.312 ⫻ 10⫺3 mm2. [Adapted from Edman et al. (14, 15)].
descending limb of the force-length relationship (1, 21,
22).
PART 2: SINGLE-FIBER EXPERIMENTS
To test predictions of the cross-bridge theory associ-
ated with the force-length relationship, strict criteria
must be adhered to: the sarcomere length must be
isometric, and activation of the muscle must be maxi-
mal. When muscle contracts under conditions that do
not comply with these conditions, muscle length still
has an effect on the magnitude of the contractile
response, but the predictions of the cross-bridge theory
will not necessarily be confirmed. In this section, the
force-length properties of single skeletal muscle fibers
are described, and the length dependence of the contrac-
tile response is considered when these strict criteria
(isometric sarcomeres and maximal activation) are not
present.
Force-length relationship. To ensure isometric condi-
tions of sarcomeres while the muscle fiber force-length
properties are studied, feedback control of sarcomere
length is necessary. This can be approximated by
control of a segment of the fiber length. Gordon et al.
(28) used segment length control in their classic study
of the force-length properties of isolated fibers of frog
skeletal muscle. These authors used a spot follower
device and servo control to maintain a constant dis-
tance between two markers on a short segment of the
muscle fiber. Even with segment length control, there is
some uncertainty that sarcomere length remains con-
stant throughout the tetanic contraction. Redistribu-
tion of sarcomere length was thought to occur after the
rapid rise of tension, and this redistribution of sarco-
mere length was coincident with a slow rise in tension
referred to as tension creep.
Gordon et al. (28) were the first to describe the
force-length properties of skeletal muscle sarcomeres.
They reported that peak active tension during the rapid
rise of tension was constant across a sarcomere length
Downloaded from jap.physiology.org on April 4, 2005
range from 2.0 to 2.2 µm. At progressively longer
sarcomere lengths, active tension decreased linearly,
reaching zero at 3.6 µm (Fig. 2). This segment of the
force-length relationship is referred to as the descend-
ing limb. When sarcomere length was ⬍2.0 µm, devel-
oped tension was less than the peak value, decreasing
linearly to a sarcomere length of ⬃1.7 µm and decreas-
ing more steeply at even shorter sarcomere lengths
(ascending limb). These observations are consistent
with predictions based on the cross-bridge and sliding
filament theories of muscle contraction.
Edman and Reggiani (17) observed a force-length
relationship that was slightly different from that re-
ported by Gordon et al. (28). They observed a sigmoidal
decline in developed tension on the descending limb of
the force-length relationship and suggested that this
sigmoidal rather than linear decrease in force was
consistent with small sarcomere length nonuniformi-
ties within the length-controlled segment. They argued
that such a distribution of sarcomere lengths might
diminish the magnitude (width) of the plateau region of
the force-length relationship and may permit some
force development in the fiber at a mean sarcomere
length that is ⬎3.6 µm.
Although there are minor discrepancies in the re-
sults of studies that have used a segment length-
control approach, the general findings are the same and
they support the cross-bridge theory of muscle contrac-
tion (16, 17, 29, 31, 47).
Fixed-end muscle contractions. In circumstances
where sarcomere or segment length-control is not used,
the term ‘‘fixed-end contraction’’ is appropriate. In this
type of experiment, ‘‘isometric’’ refers to the muscle
(fiber) tendon unit, since only the distance between the
fixed ends remains constant. In addition to changes in
sarcomere length during the slow change in developed
tension (creep), there can be rapid adjustments of
sarcomere length due to stretching of compliant struc-
tures in series with the fiber. Under these circum-
stances, there is still a length dependence of developed
 INVITED REVIEW
tension. Some investigators have reported a shape of
the apparent force-length relationship quite similar to
the force-length relationship described above (48, 82).
However, others have reported differences in the shape
of the length-dependance of force in fixed-end contrac-
tions, compared with the shape found with length-
controlled contractions. The plateau of the relationship
is more curved and extends to longer sarcomere lengths
in fixed-end experiments than in length-controlled ex-
periments. This extended plateau results in greater
forces at any given average sarcomere length on the
descending limb than those obtained by using length-
controlled experiments (31, 82), giving a length depen-
dence of active force that is situated to the right,
relative to the length-controlled force-length relation-
ship (Fig. 6). The difference in the descending limb
between theoretical and experimental studies has been
a focus of criticism of the sliding filament theory by
Pollack (68–70) and ter Keurs et al. (82). However, it is
recognized that nonuniform sarcomere lengths may
account for this difference and it is not appropriate to
discard the cross-bridge theory based on the results of
experiments with fixed-end contractions.
Hill (38) was the first to propose that, when a muscle
is stimulated to contract at a long length, redistribution
of segment lengths occurs, and he suggested that this
redistribution was responsible for the slow phase of rise
in force tension (creep) during a tetanic contraction.
This idea was advanced by Gordon et al. (28, 29), who
proposed more specifically that tension creep was caused
by a redistribution of sarcomere lengths during a
tetanus, and that this redistribution would cause an
increase in sarcomere length nonuniformity. In a series
of experiments, Edman and Reggiani (16, 17) provided
evidence that sarcomere length is not generally uni-
form along the length of an isolated muscle fiber,
neither at rest nor during activation. At rest, in highly
Fig. 6. Predicted force-length relationship (plateau and linear de-
crease in active force) and representation of active force for fixed-end
contractions of mouse extensor digitorum longus fiber bundles (curved
line). max, Maximum. [Adapted from Rassier (73).]
1449
stretched fibers, sarcomere lengths are shorter near the
ends compared with the middle of fibers (9, 42, 49).
During contraction at long lengths, sarcomeres situ-
ated near the ends of the fibers were found to shorten,
whereas sarcomeres in central parts of the fiber were
found to be stretched (16, 17). The important question
is, How can nonuniformity of sarcomere length permit
greater force development on the descending limb?
Assuming that each sarcomere follows a force-length
relationship according to the cross-bridge theory and
that sarcomere lengths are nonuniform, then long
sarcomeres will be weaker than short sarcomeres on
the descending limb of the force-length relationship.
Therefore, on activation, long (weak) sarcomeres should
lengthen, and short sarcomeres should shorten. Be-
cause the ends of the fiber are fixed, the average
velocity of sarcomere length change must be zero.
Considering the simplest case (2 sarcomeres in series),
the velocity of lengthening of one sarcomere will be
equal to the velocity of shortening of the other one, and
the force transmitted across the sarcomeres will be
Downloaded from jap.physiology.org on April 4, 2005
equal. Considering that the slope of the eccentric side of
the force-velocity relationship is steeper than that of
the concentric side means that the force transmitted
across these two sarcomeres in series will be much
closer to the isometric force of the shorter (stronger,
shortening) sarcomere, than to the force for the ‘‘aver-
age’’ isometric sarcomere length (63, 64). Therefore, the
force at any average sarcomere length beyond the
sarcomere length of optimal overlap of the myofila-
ments will be greater for fixed-end contractions than
the force predicted by cross-bridge theory, for that
(average) sarcomere length.
This explanation of the enhanced force on the descend-
ing limb of the length-tension relationship of skeletal
muscle requires that individual sarcomeres will con-
tinue to change length, resulting in increased inhomo-
geneity (16) and increased isometric tension during a
tetanic contraction. This increasing tension is thought
to be the tension creep that has commonly been ob-
served. It has been predicted that when individual
sarcomeres shorten to a length less than the optimum
(to the ascending limb of the force-length relationship),
they will eventually reach a length where the isometric
force of the sarcomere is equal to the force transmitted
across the sarcomeres, and shortening will stop (64).
Another potential explanation for the enhanced iso-
metric force on the descending limb exists. It is known
that stretch of a muscle fiber results in a permanent
enhancement of active force above that predicted for an
isometric contraction at the new length (14, 15) and
that shortening has the opposite effect (13). This effect
of stretch has been referred to as stretch-induced force
enhancement (14, 15). Although these force modula-
tions may also be attributed to inhomogeneity of sarco-
mere lengths (18, 47, 62), these modulations could be a
property of individual sarcomeres.
Submaximal contractions. The shape of the force-
length relationship and the length-dependence of force
development in fixed-end contractions, as described
above, was determined in single muscle fibers that
1450 INVITED REVIEW
were maximally activated (tetanic contractions). When
the stimulation is at a subfusion frequency, activation
is submaximal, and the shape of the length-dependence
of force development is not the same as for maximal
contractions (3, 71). In particular, during submaximal
levels of stimulation, peak active tension occurs at a
length longer than the length associated with maximal
overlap of the myofilaments (79).
During submaximal contractions, greater force is
obtained when the number of available cross bridges is
reduced by an increase in muscle length. This property
of muscle appears to be associated with enhanced
activation at long muscle lengths and has been referred
to as length-dependent activation (16, 53, 78). The term
‘‘activation’’ has been used in many different ways in
the skeletal muscle literature, for example, to indicate
the relative frequency of stimulation or frequency of
membrane action potentials of a muscle or motor nerve
(5); to reflect the intracellular levels of free Ca2⫹ (4); or
to reflect the proportion of troponin C with Ca2⫹ bound
(2), among others. In general, this term is used to
indicate a change of state from inactive to active and is
often coupled with an implication of relative amplitude
(‘‘level of activation’’). For this reason, the term ‘‘muscle
activation’’ is defined here as the proportion of troponin
C with Ca2⫹ bound.
The isometric developed tension in a submaximally
activated, single skinned skeletal muscle fiber is deter-
mined by the following: average overlap of the myofila-
ments, free Ca2⫹ concentration, and the force-Ca2⫹
relationship (Fig. 7). Factors affecting Ca2⫹-binding
kinetics alter the proportion of troponin C that is
occupied by Ca2⫹ at a given free Ca2⫹ concentration. In
an intact cell, the frequency and magnitude of Ca2⫹
oscillations (10) will affect the extent of Ca2⫹ binding to
Fig. 7. Force-pCa2⫹ relationships. The 2 curves represent normal
situation on the right and increased Ca2⫹ sensitivity (shift to left).
Curves were drawn from published values for the Hill equation
presented by Martyn et al. (58) for skinned twitch fibers of a frog
muscle at 2.4- (right) and 3.1-(left) µm sarcomere lengths.
troponin C. Therefore, the level of activation depends
on the time history of Ca2⫹ transients. However, the
kinetics of Ca2⫹ binding to troponin C and of cross-
bridge interaction have a damping effect on the relation-
ship between intracellular Ca2⫹ concentration and ac-
tive force, since oscillations in force at a given frequency
of stimulation are smaller than oscillations in free Ca2⫹
concentration. The force developed at a given average
free Ca2⫹ concentration and a given magnitude of
myofilament overlap depends on the proportion of Ca2⫹
binding sites that are occupied and on the kinetics of
cross-bridge interaction. The kinetics of cross-bridge
interaction can be considered, in the simplest case, to
be governed by two rate constants (f and g; the rates of
attachment and detachment of cross bridges, respec-
tively). For the case in which there is a large constant
number of identical attachment possibilities [i.e., cross
bridges with identical x-values (40) at each instant in
time], the proportion of attached cross bridges (n) will
be a function of time exclusively; i.e.
Downloaded from jap.physiology.org on April 4, 2005
dn
⫽ (1 ⫺ n) f (x) ⫺ ng(x)
dt
For the specific state of dynamic equilibrium, when
dn/dt ⫽ 0, the value for the proportion of attached cross
bridges, neq, becomes
f (x)
neq ⫽
f (x) ⫹ g(x)
Attempts to measure Ca2⫹ binding to troponin during
skeletal muscle activation have failed to demonstrate a
length dependence of Ca2⫹ affinity of troponin (25, 67,
86, 87). Furthermore, the increase in force at long
lengths during submaximal stimulation has been ob-
served in skinned fiber preparations (20), so it is not
dependent on an enhancement of the free Ca2⫹ concen-
tration. Furthermore, Balnave and Allen (3) have shown
that, for the mouse flexor digitorum brevis muscle,
average free Ca2⫹ concentration is independent of
length for a given low frequency of stimulation.
Studies using skinned fiber preparations have shown
that when free Ca2⫹ concentration is submaximal there
is more relative active force developed at long than at
short sarcomere lengths. This result implies that there
is a leftward shift in the force-Ca2⫹ relationship when
the muscle is stretched to lengths beyond optimum (19,
20, 59, 61, 80). This property of skeletal muscle is
illustrated in Fig. 7. The force-Ca2⫹ relationship has
been used as an indicator of Ca2⫹ sensitivity (59, 79). A
leftward shift of the force-Ca2⫹ relationship represents
increased sensitivity, and a rightward shift represents
decreased sensitivity. At long sarcomere lengths, the
Ca2⫹ sensitivity is increased, but activation is not
affected. Therefore, the increased Ca2⫹ sensitivity at
long sarcomere lengths is likely caused by changes in
cross-bridge kinetics. It is believed that changes in
intermyofilament spacing, as a consequence of changes
in muscle length, may be responsible for these altered
cross-bridge kinetics and, therefore, length-dependent
changes in Ca2⫹ sensitivity (24, 25, 65, 67, 87).
 INVITED REVIEW
It has been shown that intermyofilament spacing
decreases as skeletal muscle is stretched (60, 74, 75).
Using skinned fibers of rabbit soleus, Godt and
Maughan (26) confirmed that compression of the myo-
filament lattice at short sarcomere length with high-
molecular-weight dextran resulted in enhanced Ca2⫹
sensitivity (leftward shift in the force-Ca2⫹ relation-
ship). These results have been confirmed by other
investigators (12, 81, 87). Because compression of the
lattice can enhance Ca2⫹ sensitivity, and the myofila-
ment lattice is compressed at long lengths, it is reason-
able to assume that lattice compression is responsible
for the length-dependent increase in Ca2⫹ sensitivity.
The specific conditions within the myofilament space
that affect length dependence of Ca2⫹ sensitivity are
unknown. One explanation that has been offered is that
proximity of the myofilaments enhances the probability
of cross-bridge interaction (26). This enhanced probabil-
ity would be expected to increase the rate constant for
cross-bridge attachment, f(x). If rate of detachment,
g(x), remains unaffected by intermyofilament spacing,
an increase in f(x) would effectively result in a greater
number of cross bridges being engaged during a contrac-
tion and thus enhance the amount of tension produced.
PART 3: ISOLATED WHOLE MUSCLE
It is difficult to use the segment or sarcomere length
control approach to the study of the force-length proper-
ties of whole isolated or semi-isolated muscles. There-
fore, we will not discuss segment-controlled experi-
ments in this section, and the results of experiments
with whole muscle will be described as the length-
dependence of active force.
Rack and Westbury (71) found an extended plateau
in the length dependence of active force for tetanic
contractions in cat soleus muscles. The developed force
did not start to decrease significantly until a muscle
length corresponded to an average resting sarcomere
length of ⬃3.0 µm. The extended plateau of the length-
dependence of active force could be caused by elastic
elements in series with the muscle fibers that allow for
sarcomere shortening to a length much less than the
resting sarcomere length.
Close (11) reported a length dependence of force in
whole muscle, similar to the force-length relationship
observed by those using segment control in single fibers
(17, 28, 31); i.e., the force decreased linearly with
decreasing filament overlap on the descending limb of
the force-length relationship. Close (11) minimized the
effect of series elastic elements that may have permit-
ted better agreement between the active and passive
sarcomere lengths than had been obtained by others
(57).
Submaximal contractions. As in studies with single
cells, studies with whole muscles revealed that the
length dependence of force varies with different levels
of muscle stimulation. The results of these studies
showed that the optimal length for twitch contractions
(11, 71, 76) and submaximally activated muscle (76)
was shifted to longer muscle lengths than would be
1451
predicted according to the cross-bridge theory. Presum-
ably, the same mechanism responsible for this shift in
single fibers can explain this shift in whole muscles.
Distribution of sarcomere lengths. When the relation-
ship between length and developed tension is assessed
in a multicellular preparation, one must ask whether
the mean sarcomere length in one cell is the same as in
an adjacent cell. Differences in mean sarcomere length
between adjacent fibers could occur because of different
numbers of sarcomeres in series for fibers of a given
length or because of differences in the fiber-to-tendon
length ratio over a given length of muscle. It has been
reported that sarcomere length variation is greater in a
bundle of fibers than in a single fiber (66). If fibers
within a given muscle have different average sarco-
mere lengths at a given muscle length, peak force
would be reduced and the plateau would be broader,
compared with fibers of identical sarcomere lengths
within a given muscle.
The distribution of sarcomere length across fibers
appears to be greater for the rat extensor digitorum
Downloaded from jap.physiology.org on April 4, 2005
longus than for the rat medial gastrocnemius muscle
(39), which might explain the relative broadening of the
relationship between developed force and muscle length
for the extensor digitorum longus. It has also been
found that the optimal length of individual motor units
varies within a given muscle (23, 54), suggesting that,
at a given muscle length, different motor units have
different mean sarcomere lengths.
PART 4: FUNCTIONAL IMPLICATIONS
In the previous parts of this review, we were con-
cerned with the force-length properties and the length
dependence of force production in isolated skeletal
muscles, fibers, or sarcomeres. In reality, muscles are
attached (typically) to bones, and they cross one or
more joints at which they function to produce move-
ments. The forces exerted by muscles create a moment
about the joint(s).
When considering the force-length characteristics of
a muscle in its anatomic environment, two factors
should be considered when evaluating the potential of
the muscle to produce movements: the moment arm of
the muscle about the target joint and the excursion
of the muscle. The moment arm of the muscle deter-
mines the moment (Mj ) produced about a joint by
muscular contraction since
Mj ⫽ r ⴛ F
where r is the location vector from the center of the
joint to any point on the line of action of the muscle
force, F is the muscle force (vector), and ⴛ represents
the vector cross product (Fig. 8A). For two-dimensional
considerations, the above equation may be written in
its scalar form as
Mj ⫽ d · f
where Mj is the magnitude of the moment produced by
the muscle about the target joint, d is the perpendicular
distance (moment arm) from the joint center to the line
1452 INVITED REVIEW
Fig. 8. Schematic representation of a muscle and its moment arm
crossing a single joint. Illustrated in A is the force vector (F) and its
line of action. Also shown is the location vector, r, showing the
distance from center of the axis of rotation to the line of action of the
muscle. In a 2-dimensional consideration, the moment about the axis
of rotation, which is due to the muscle, is given by d · f, as shown in B.
See text for further description.
of action of the muscle force, and f is the magnitude of
the muscle force (Fig. 8B).
The importance of the moment arm may be illus-
trated in an example with two muscles of identical
force-length properties crossing the same joint, but
their moment arms are different by a factor of two (Fig.
9). If we assume that muscle B has a moment arm twice
that of muscle A, it is obvious that muscle B can exert a
peak moment twice that of muscle A. However, the
larger moment arm of muscle B compared with A
causes a larger change in length of muscle B compared
Fig. 9. Schematic representation of 2 muscles (A and B) crossing a
single joint. Both muscles are identical in all aspects, except muscle B
has a moment arm twice that of muscle A.
with muscle A for a given change in joint angle;
therefore, muscle B has only one-half the range of
active force production (in terms of joint angular dis-
placement) compared with muscle A (Fig. 10).
Because the moment-angle relationship of a muscle
about a joint is determined by the force-length proper-
ties of the muscle and the variable moment arm, the
following three basic scenarios relating force and mo-
ment arm to the joint moment are possible (Fig. 11): 1)
the moment arm is about constant throughout the
range of joint motion; therefore, the shape of the
moment-angle relation reflects the shape of the force-
length relation accurately (Fig. 11A); 2) the moment
arm is decreasing (increasing) as the force potential of
the muscle is increasing (decreasing); therefore, the
moment-angle relation is flattened compared with the
force-length relation (Fig. 11B); and 3) the moment arm
is increasing (decreasing) as the force potential is
increasing (decreasing), therefore the moment-angle
relation is an enhanced version of the force-length
relation (Fig. 11C). Depending on the exact relation
Downloaded from jap.physiology.org on April 4, 2005
between the force-length property of the muscle and
the corresponding moment arm, the joint angle of
maximal muscle force may not correspond to the joint
angle of maximal moment.
Excursion is defined as the change in length of a
muscle when going through the full anatomical range
of joint motion (i.e., longest to shortest in situ length).
Intuitively, one might assume that a muscle is attached
to the musculoskeletal system such that it operates
essentially at or around its optimal length (i.e., a length
at which it is strongest). However, this assumption is
not correct. Most muscles whose in situ force-length
properties have been determined appear to operate
primarily on the ascending or descending limb of the
force-length relationship, reaching the plateau toward
Fig. 10. Schematic force-length relationship of muscles A and B from
Fig. 9. Although muscles A and B were assumed to have identical
physiological cross-sectional areas and fiber lengths, their moment-
joint angle relations differ substantially because of their difference in
moment arm length (see d in Fig. 8). Muscle B (with the large
moment arm) will produce a larger moment for a given muscle force
than will muscle A; however, muscle B has a larger excursion than
muscle A for a given change in joint angle; therefore, its active range
of force production (b) is smaller than that of muscle A (a).
 INVITED REVIEW
the end of the range of joint motion. For example, the
cat soleus, gastrocnemius, and plantaris muscles have
all been found to work primarily on the ascending limb
of the force-length relationship (34, 71). Similarly,
human gastrocnemius muscles operate primarily on
the ascending limb of the force-length relationship (35).
However, frog semitendinosus appears to occupy the
Fig. 12. Schematic representation of a force-fiber length relationship
and a muscle undergoing a stretch-shortening (loop on left) and a
shortening-stretch (loop on right) cycle.
1453
Fig. 11. Force- (solid line) and moment- (dashed
line) joint angle (␣) relationships for a muscle with 3
different (A-C) moment arm (r)-joint angle relation-
ships.
Downloaded from jap.physiology.org on April 4, 2005
descending limb of the force-length relationship during
everyday use (56).
The question that arises is, Why do different muscles
occupy different parts of the force-length relationship
in vivo? The answer to this question is not known;
however, it appears likely that there is some connection
between the functional demands of a muscle and the
region of the force-length relationship it occupies. For
Fig. 13. Active (a), passive (p), and total (t) force-length relationships
for frog gastrocnemius, sartorius, and semitendinosus muscles
[Adapted from Wilkie (88).]
1454 INVITED REVIEW
Fig. 14. Schematic representation of the in vivo force-joint angle relationships of human rectus femoris for normal
subjects (A), high-performance runners (B), and cyclists (C).
example, during everyday movement tasks, muscles
undergo either a stretch-shortening or a shortening-
stretch cycle. In a stretch-shortening cycle, a muscle is
stretched initially as it increases its force and then
shortens as it decreases its force (Fig. 12). Such a
function follows a ‘‘force vs. length’’ curve with positive
slope, similar to that of the ascending limb of the
force-length relationship. During a shortening-stretch
cycle, a muscle shortens first as it develops force and
then is stretched as its force decreases. This function
follows a negative force vs. length plot, similar to the
descending limb of the force-length relationship.
For the few muscles for which functional and in vivo
force-length properties are known, it appears that
muscles undergoing stretch-shortening cycles during
normal movements operate on the ascending part [cat
and skunk triceps surae, plantaris, and human gastroc-
nemius (30, 34, 35, 71)], and muscles undergoing
shortening-stretch cycles operate on the descending
part of the force-length relationship [frog semitendino-
sus (56)]. It is also worth noting that muscles that
operate on the ascending part of the force-length rela-
tionship tend to have a passive force that appears at
short muscle length, whereas muscles that operate on
the descending part tend to have passive forces that
appear only at long muscle length (Fig. 13).
Fig. 15. Schematic representation of 2 muscle fibers of equal length.
One fiber contains more sarcomeres in series than the other; there-
fore, its average sarcomere length is smaller than that of the fiber
with the fewer sarcomers. If the number of sarcomeres in the 2 fibers
at a given length is sufficiently different, then one fiber might be
operating on the ascending limb and the other on the descending limb
of the force-length relationship.
Up until now, the force-length property of skeletal
muscle has been considered as a given, constant charac-
teristic. However, muscles have a tremendous ability
for adaptation. Therefore, the question arises, Do in
vivo force-length properties adapt to changes in every-
day requirements, changes that might be produced, for
example, by chronic training or tendon transfer sur-
Downloaded from jap.physiology.org on April 4, 2005
gery?
In a study aimed at determining the in vivo force-
length properties of human rectus femoris muscles, we
made the following observations (Fig. 14): the force-
length curve for normal subjects was centered around
optimal length (Fig. 14A) (36), whereas the force-length
curves of national caliber runners and cyclists fell on
the ascending and descending limb of the force-length
relationship, respectively (Fig. 14, B and C) (32). Al-
though the sample size for the different groups was
small (n ⫽ 9, 4, and 3 for normal subjects, runners, and
cyclists, respectively), the force-length regression lines
for the runners and cyclists were statistically (␣ ⫽ 0.05)
different from zero, whereas those of the normal sub-
jects were not.
There is a variety of possible explanations for why
the force-length properties for the runners were differ-
ent in shape from those of the cyclists; the most
appealing reason is an adaptation of the number of
sarcomeres arranged in series in the muscle fibers.
Following this argument, one would assume that the
Fig. 16. No. of sarcomeres arranged in series in superficial and deep
portions of rabbit tibialis anterior (TA) muscle. c, Control animals, no
retinacular release; s, sham-operated animals, no retinacular re-
lease; r, experimental animals, retinacular release. * Release group,
significantly different from control and sham-operated groups, P ⬍
0.01 (51).
 INVITED REVIEW
number of sarcomeres in series in rectus femoris muscle
fibers of runners is larger than in cyclists; therefore, for
a given joint configuration, the average sarcomere
length of the runners would be smaller than that of the
cyclists (Fig. 15). Whether this type of adaptation really
occurred in the top athletes could not be evaluated.
In an attempt to determine whether the number of
sarcomeres arranged in series within muscle fibers
would adapt to tendon transfer procedures, the follow-
ing study was performed (50, 51). The tendon of the
rabbit tibialis anterior was released from its retinacu-
lar constraint at the ankle. For the experimental
animals (retinacular release), the origin to insertion
distance of the tibialis anterior (and, therefore, its
passive force) became smaller, but the moment arm
about the ankle (and, therefore, its excursion) became
larger than it was for the control animals (no surgery or
sham surgery). If active or passive forces were the
primary positive modulators of the number of in series
sarcomeres, one would expect to see a decrease in the
number of sarcomeres in the experimental compared
with the control muscles; if, however, excursion was the
primary positive modulator, one would expect an in-
crease in the number of sarcomeres.
After 8 wk of retinacular release of the tibialis
anterior muscles, it was found that in these growing
rabbits (4–12 wk) the number of sarcomeres in series
was significantly increased in the experimental com-
pared with the control and sham-control animals (Fig.
16). Therefore, it was concluded that a (small) change
in tendon path (a ‘‘tendon transfer’’) that causes changes
in the origin to insertion distance and moment arm of
the target muscle can cause adaptation in the number
of sarcomeres arranged in series in a muscle fiber. Such
a change in sarcomere number also changes the shape
of the length-tension curve. Specifically, a muscle with
an increased number of sarcomeres in series is able to
produce active force over a larger range of muscle
length than a corresponding muscle with fewer sarco-
meres.
Varying the type of exercise has also been shown to
influence sarcomere number. Lynn and Morgan (55)
studied vastus intermedius fibers of rats trained with
uphill or downhill running. They found that the rats in
the downhill-running group had significantly more
sarcomeres arranged in series in the vastus interme-
dius fibers than the rats in the uphill-running group,
indicating that skeletal muscle is able to adapt sarco-
mere number to the movement (exercise) demands.
Summarizing, it is not trivial to determine the length
dependence of force of in vivo human skeletal muscles.
Aside from problems associated with controlling maxi-
mal effort, voluntary contractions, and isolating the
force of a single muscle from the total force of an agonist
group (issues that were not addressed here), force-
length properties can and will adapt to the functional
requirements imposed on the muscle. In vivo, the
force-length properties of muscles manifest themselves
as moment-joint angle relationships that are more
complex than the force-length relationships because of
the nonlinearities that exist between force and moment
1455
as well as between muscle length and joint angle. These
nonlinearities are directly associated with the variable
moment arm of the muscle force vector about the target
joint. Therefore, moment arm determination or, equiva-
lently, the determination of the instantaneous joint
axis and line of action of the muscle become of utmost
importance when determining the in vivo force-length
properties of muscles. However, the in vivo determina-
tion of these factors is often difficult and sometimes
impossible.
D. E. Rassier was supported, as a graduate student, by Centro de
Aperfeicoamento de Pessoal de Ensino Superior (Brazil).
Present address of D. E. Rassier: Escola de Educacao Fisica,
Laboratorio de Pesquisa do Exercicio (LAPEX), Rua Felizardo 750,
Bairro Jardim Botanico, Porto Alegre (RS), Brazil.
Address for reprint requests and correspondence: B. R. MacIntosh,
Human Performance Laboratory, Faculty of Kinesiology, The Univer-
sity of Calgary, Calgary, AB, Canada T2N 1N4 (E-mail:
brian@kin.ucalgary.ca).
Received 22 May 1998; accepted in final form 23 December 1998.
Downloaded from jap.physiology.org on April 4, 2005
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