See

discussions, stats, and author profiles for this publication at: https://www.researchgate.net/publication/46304281

Muscle fascia and force transmission

Article in Journal of bodywork and movement therapies · October 2010

DOI: 10.1016/j.jbmt.2010.01.005 · Source: PubMed

CITATIONS READS

62 406

1 author:

Peter Purslow
National University of Central Buenos Aires
116 PUBLICATIONS 3,806 CITATIONS

SEE PROFILE

Some of the authors of this publication are also working on these related projects:

New Aspects of Meat Quality - from genes to ethics View project

All content following this page was uploaded by Peter Purslow on 27 February 2014.

The user has requested enhancement of the downloaded file. All in-text references underlined in blue are added to the original document
and are linked to publications on ResearchGate, letting you access and read them immediately.
Journal of Bodywork & Movement Therapies (2010) 14, 411e417

available at www.sciencedirect.com

journal homepage: www.elsevier.com/jbmt

FASCIA PHYSIOLOGY

PREVENTION & REHABILITATIONdFASCIA PHYSIOLOGY

Muscle fascia and force transmission
Peter P. Purslow, PhD

Department of Food Science, University of Guelph, Guelph, Ontario N1G 2W1, Canada

Received 13 October 2009; received in revised form 3 January 2010; accepted 7 January 2010

KEYWORDS Summary This paper reviews the major intramuscular extracellular matrix (IM-ECM) struc-
Muscle; tures (endomysium, perimysium and epimysium) and their possible mechanical contributions
Connective tissue; to muscle functions. The endomysium appears to provide an efficient mechanism for transmis-
Extracellular matrix; sion of contractile forces from adjacent muscle fibres within fascicles. This coordinates forces
Mechanical function; and deformations within the fascicle, protects damaged areas of fibres against over-extension,
Myofascial force and provides a mechanism whereby myofibrils can be interrupted to add new sarcomeres
transmission; during muscle growth without loss of contractile functionality of the whole column. Good
Endomysium; experimental evidence shows that perimysium and epimysium are capable in some circum-
Perimysium; stances to act as pathways for myofascial force transmission. However, an alternative role
MMPs; for perimysium is reviewed, which involves the definition of slip planes between muscle fasci-
ECM turnover cles which can slide past each other to allow large shear displacements due to shape changes
in the whole muscle during contraction. As IM-ECM is continually remodelled so as to be me-
chanically adapted for its roles in developing and growing muscles, control of the processes
governing IM-ECM turnover and repair may be an important avenue to explore in the reduction
of fibrosis following muscle injury.
ª 2010 Elsevier Ltd. All rights reserved.

Introduction pathways by which IM-ECM is remodelled and adapted due

The soft connective tissues associated with muscle tissue
have been referred to as the intramuscular extracellular
matrix (IM-ECM), intramuscular connective tissue (IMCT)
and muscle fasciae (MF). Although these general names can
be used interchangeably, the term IM-ECM will be used
here. Substantial reviews of the structure, development,
composition and function of IM-ECM exist (Purslow and
Duance, 1990; Purslow 2002, 2008). The mechanisms and
to changing functional demands during muscle growth and
repair, and in response to exercise training or disuse, are
addressed by Kjær and Magnusson (2008). Like most other
soft connective tissue structures, the amount and compo-
sition of IM-ECM structures are not simply programmed
during embryogenesis and subsequent post-natal matura-
tion processes. The amounts and composition of the various
IM-ECM structures in living tissue represent a dynamic
balance between deposition, growth, remodelling and
degradation, which is affected by the interplay between

E-mail address: ppurslow@uoguelph.ca

1360-8592/$ - see front matter ª 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.jbmt.2010.01.005
 412
functional demands on the tissue and the mechanical
environment. The cellular mechanisms of mechano-
transduction in fibroblasts are reviewed by Chiquet et al.
(2009). The purpose of the current review is to highlight
information pointing to the crucial roles of IM-ECM in force
transmission and accommodation of shape changes in
functioning muscle.
General structure and biochemical
PREVENTION & REHABILITATION dFASCIA PHYSIOLOGY
composition of IM-ECM
As schematically shown in Fig. 1, each muscle is surrounded
by epimysium, a connective tissue layer that is continuous
with the tendons that attach the muscles to the bones. In
some long strap-like muscles the epimysium is composed of
two parallel sets of wavy collagen fibres in a crossed-ply
arrangement, embedded in a proteoglycan matrix (see
Fig. 2). When the muscle is at its resting length, the two
sets of collagen fibres are arranged at angles of approxi-
mately 55 to the long axis of the muscle fibres. In other
muscles, and especially in pennate muscles, the arrange-
ment of collagen fibres in the epimysium is parallel to the
long axis of the muscle and forms a dense surface layer that
functions as a surface tendon. The perimysium is a contin-
uous network of connective tissue which divides the muscle
up into fascicles or muscle fibre bundles. Fascicles run
along the length of the muscle from tendon to tendon, and
the ends of muscle fibres form highly folded interdigitating
joints (the myotendinous junction) with the tendon at this
point (Trotter, 1993). The perimysial network merges into
the epimysium at the surface of the muscle and is
mechanically connected to it. Within each fascicle or
muscle fibre bundle, the endomysium is a continuous
network of connective tissue that separates individual
muscle fibres.
Each of the epimysium, perimysium, and endomysium
layers has its own structure and composition, but generally
these connective tissue layers are composed of collagen
fibres in an amorphous matrix of hydrated proteoglycans
(PGs) which plays a crucial role in mechanically linking
Fig. 1 Schematic diagram of IM-ECM structures in a skeletal
muscle. Epimysium delineates the surface of the muscle,
perimysium separates muscle fascicles and endomysium sepa-
rates individual muscle fibres. Also depicted are the contractile
myofibrils within each muscle fibre. (Artwork: Dr. L.-T. Lim).
P.P. Purslow
Fig. 2 Light micrograph of epimysium from bovine sterno-
mandibularis muscle, showing arrangement of collagen fibres
in crossed-plies. The fibres are in two parallel layers lying at
þ55 and 55 to the muscle fibre axis. From Purslow (1999),
with permission. In epimysium from other muscles the collagen
is more aligned with the muscle fibre direction and acts as an
exo-tendon or aponeurosis.
together the collagen fibre networks in these structures
(Scott, 1990). Listrat et al. (1999, 2000) show that collagen
types I, III, IV, V, VI, XII and XIV are all expressed in muscle
development. Collagen typically represents 1e10% of the
dry weight of adult skeletal muscle (Bendall, 1967). Fibres
of elastin can be found in the IM-ECM of some muscles,
principally in the perimysium. However, the amount of
elastin is small in most muscles and is typically less than 1%
of muscle dry weight (Bendall, 1967).
Collagen fibres are stabilised by the formation of cova-
lent crosslinks directed by a clear set of post-translational
modifications which act on the collagen molecules extra-
cellularly after assembly of the collagen molecules into the
quarter-stagger overlapped arrangement characteristic of
fibrils (Bruns and Gross, 1973). The formation of crosslinks
is essential for the mechanical strength and stiffness of
collagen fibres (Bailey et al., 1998). During gestation and
post-natal maturation there are changes in the types and
amounts of covalent crosslinks that stabilise the collagen
molecules within all connective tissues in the body,
including IM-ECM. There are also non-enzymatic reactions
of collagen with glucose and other aldehydes. Formation of
additional crosslinks through advanced glycation end
products (AGEs) is typical of the changes in connective
tissues in diabetes and during ageing and glycation, and is
thought to be a significant contributor to changes in the
mechanical properties of connective tissues with age (Paul
and Bailey, 1996). Advanced glycation end products can be
incorporated into the body from dietary sources (e.g. heat
processing of some foods creates AGEs) and from tobacco
smoke (Avery and Bailey, 2008). In this way, diet and life-
style may affect the mechanical properties of IM-ECM via
AGE-cross-linking of collagens.
IM-ECM changes during muscle development
During embryonic development of intramuscular connec-
tive tissue, the amounts of the various collagens and PGs
Muscle fascia and force transmission
changes (Velleman et al., 1999; Listrat et al., 1999; Lawson
and Purslow, 2001). Spatial variations between the endo-
mysium and perimysium within one muscle (Nishimura
et al., 1997) and differences in expression of both collagen
type I and PG components such as laminin between muscles
(Lawson and Purslow, 2001) are both determined early in
prenatal development. In bovine muscles, type I collagen
expression is always higher than type III expression at all
stages of gestation and post-natally (Listrat et al., 1999).
Thus some differences in the composition of intramuscular
connective tissue appear to be pre-programmed in
embryogenesis. However, there are some variations in the
amounts of collagens as muscle development progresses. In
bovine psoas and triceps muscles the total collagen
concentration and amounts of collagen type I is maximum
at the point in gestation when the expression of myosin
within muscle fibres changes from the embryonic to the
adult form (Listrat et al., 1999). After this, the growing
diameter of the muscle fibres dilutes out the connective
tissue content of the muscle. In contrast, the pectoralis and
quadriceps muscles of the chick show steady increases in
collagen type I content and laminin content through
gestation and post-natally (Lawson and Purslow, 2001).
Whether these differences between bovine and chick
muscle growth are due to avian versus mammalian phyla
differences or due to functional differences in the muscles
studied remains unclear.
The amounts and composition of endomysium
and perimysium vary between functionally
different muscles
In fully developed adult animals, there are large differences
in the amounts and composition of IM-ECM between different
muscles in the body. Histological comparison (see Fig. 4 in
Purslow, 2005) illustrates that the continuous perimysial
network surrounds or separates fascicles of radically
different sizes and shapes in different muscles from the same
animal. This difference also results in different thicknesses of
perimysial connective tissue. A comparison of the connective
tissue content of 14 bovine muscles shows that the endomy-
sial collagen content is between 0.47% and 1.2% of dry weight,
but the perimysial collagen content in the same muscles
ranges from 0.43% up to 4.6% of dry weight (Purslow, 1999).
The amount of perimysium in muscles varies far more than the
amount of endomysium. These variations, especially in the
amount and spatial organisation of the perimysium have long
been taken to show that IM-ECM must play strong roles in the
normal physiological functioning of each muscle. As reviewed
in the following two sections, some possible explanations of
these roles are emerging but are far from complete.
Structure and functional roles of the
endomysium
As reviewed by Purslow and Duance (1990), each muscle
cell is surrounded by its own plasmalemma and basement
membrane. Filling the intervening region between the
basement membranes of two adjacent muscle cells is the
much more substantial reticular layer, which is comprised
413
of a network of collagen fibrils and fibres in a proteoglycan
matrix.
The thickness of the endomysium as a whole varies with
muscle length, becoming thicker at short muscle lengths
and thinner as the muscle is extended (see Trotter and
Purslow, 1992). Transmission electron micrography of intact
endomysium in situ confirms that all of the collagen fibres
in the network layer lie in the plane of the layer (Trotter
and Purslow, 1992). The only location where this does not
hold true is in the junction zones between the perimysium
PREVENTION & REHABILITATIONdFASCIA PHYSIOLOGY
and the endomysium of muscle cells that lie in the surface
of the fascicle.
Swatland (1975) concluded that the reticular layer was
a single structure shared between adjacent muscle cells,
and that this endomysial structure forms a continuous
network that runs across the whole muscle fascicle. This
interpretation is very strongly borne out by scanning elec-
tron microscopy of endomysial collagen networks prepared
by NaOH-extraction of muscle to remove all cell compo-
nents, PGs, plasmalemma, and basement membrane
structures (Trotter and Purslow, 1992; Purslow and Trotter,
1994; Nishimura et al., 1994, 1995; Liu et al., 1995). This
preparation technique was first demonstrated on connec-
tive tissues generally by Ohtani et al. (1988). Fig. 3 (from
Purslow and Trotter, 1994) shows such a preparation. The
structure of the endomysium appears broadly identical in
all SEM preparations from skeletal muscle from different
muscles and species, and also in cardiac muscle (Purslow,
2008).
The planar network of collagen fibres in the thick
reticular region of the endomysium is often described as
a random or quasi-random network of irregularly wavy
fibres. These collagen fibres run at almost every angle to
the muscle fibre long axis, but the network is not truly
random. Detailed image analysis of the distribution of fibre
directions with respect to the long axis of adjacent muscle
cells reveals that there is a preferred direction in the wide
distribution of collagen fibre orientations, and that this
preferred orientation changes with muscle length (Purslow
and Trotter, 1994). At short muscle lengths, more of the
collagen fibres in the endomysial network are aligned cir-
cumferentially, and at long muscle lengths there is a higher
preference for fibres to be aligned longitudinally. The
reorientation of collagen fibres in this network at short and
long muscle lengths also involves some stretching out of the
wavy fibres, but at all sarcomere lengths a very large
proportion of the collagen fibres are still wavy. The
mechanical consequence of this is that the planar network
will be very compliant in tension at all physiologically
relevant muscle lengths, and can easily deform to follow
changing muscle lengths in vivo. Although this behaviour
potentially provides overload protection at high deforma-
tions, such protection will only occur at muscle lengths well
above those experienced in normal function. These impli-
cations are confirmed by detailed modelling of the in-plane
tensile properties of the endomysium (Purslow and Trotter,
1994). Their models of the tensile properties of the endo-
mysial network are in agreement with experimental force-
length measurements by Podolsky (1964) and Magid and
Law (1985) who compared the tensile properties of relaxed
single muscle fibres with and without endomysium. The
difference that the removal of the endomysium makes to
 414
PREVENTION & REHABILITATION dFASCIA PHYSIOLOGY
Fig. 3 Scanning electron micrographs of the collagen fibre
scaffolding in IM-ECM structures in bovine sternomandibularis
muscle as revealed by NaOH-digestion of myofibrils, cytoskel-
etal proteins, cell membranes, and proteoglycans. Upper
panel; low-magnification view, showing thicker perimysial
sheets surrounding fascicles. Lower panel; high-magnification
oblique view, showing endomysial networks. From Purslow and
Trotter (1994) with permission.
the passive elasticity of single fibres is very small at phys-
iologically relevant sarcomere lengths, showing that the
endomysium is extremely compliant in tension along the
muscle fibre direction over normal working muscle lengths
in vivo.
Many muscles in species from many phyla contain muscle
fibres that do not run along the entire length of fascicles,
but terminate before reaching the myotendinous junction
(Gans and Gaunt, 1991; Trotter, 1993; Trotter et al., 1995).
Muscle fibres in series-fibred muscles are relatively short
compared to the length of the fascicle except in humans,
which appear to have relatively longer fibres in their series-
fibred muscles.
Although some intrafascicularly terminating muscle
fibres do seem to have attachments to connective tissue
P.P. Purslow
bands internal to the muscle and occasionally have myo-
muscular junctions where two muscle fibres have interdig-
itating folded joints between them, the most common
termination is a gentle tapering down to an end. These
tapering fibres have no terminating structure that would
link them directly to another muscle fibre or to the tendon
(Trotter, 1993). The fibres are staggered by about one
quarter of their length with respect to the adjacent muscle
fibres, so that the tapering end of one fibre terminates with
the endomysial network surrounding it forming a seamless
connection to the endomysium of its neighbours (Purslow
and Trotter, 1994). The endomysium is the only structure
that links muscle fibres together within fascicles. In series-
fibred muscles, transmission of tension generated in intra-
fascicularly terminating fibres to the ends of the fascicles
absolutely necessitates transmission of force through the
endomysial network, as this is the only structure continu-
ously linking the fibres (Trotter et al., 1995). Trotter and
Purslow (1992) show that the endomysium is compliant in
tension, so that force transmission is unlikely by this means,
but they also suggest that force transmission is by shear
through its thickness. The key idea is that the endomysium,
while very compliant to tensile forces acting within the
plane of the network, is much more efficient in providing
a non-compliant linkage by shear through its thickness. A
formal derivation from fibre composites theory shows that,
for practical purposes, the stiffness of the endomysium in
shear through its thickness varies only slightly with the
orientation of the collagen fibrils in the plane of the
endomysium (Purslow, 2002). Any linkage that transmits
forces from intrafascicularly terminating muscle fibres to
tendinous attachments must be non-compliant (i.e. high
stiffness) in order to be efficient. Especially in isometric
muscle contractions, any significant stretching in the length
of the fascicle due to stretchy connections would result in
a very poor transmission of contractile force. The series-
elastic nature of this shear linkage can be represented as an
apparent longitudinal stiffness Eapp (Purslow, 2002) given by
 . 2
Eapp ZG L T ð1Þ
where G is the translaminar shear modulus of the endomy-
sium, T is its thickness and L the muscle fibre length. Even if
we take a fibre as short as 1 cm in length, L/T is in the order of
2000, so that Eapp is going to be in the order of 4  106 greater
than the true translaminar shear modulus of the endomy-
sium. In a ‘‘composite’’ consisting of two parallel muscle
cells with the endomysium sandwiched between them, the
apparent longitudinal stiffness of endomysium as it deforms
in shear will still be orders of magnitude higher than the
tensile stiffness of the muscle fibres themselves. Due to this
high value of Eapp the longitudinal stiffness of the entire
assembly is going to be dominated by stretching in the muscle
fibres themselves rather than in the linking endomysium. This
shear linkage through the thickness of the endomysium
provides a force transduction pathway from one muscle cell
to its neighbours which is highly efficient. However, the
endomysium can deform easily in the plane of the network,
due to its low tensile stiffness, and so does not restrict
changes in muscle fibre length and diameter as muscles
contract and relax.
Muscle fascia and force transmission
Lateral load sharing through the endomysium is an
important concept that also explains how it is possible for
muscles to grow and to repair damaged sarcomeres. Lateral
load sharing and coordination of deformations means that
a fibre can be interrupted for the addition of new sarco-
meres necessary for muscle lengthening during growth,
without loss of function of an entire contractile column. By
the same mechanism, the contractile capacity of the
weakness of a sarcomere in which damaged myofibrils are
being broken down and remodelled during muscle repair
does not lead to tearing of the fibre at this point, as the
endomysial connections between adjacent fibres serve to
keep the strains uniform throughout the tissue. In sub-
maximal contractions not all the motor units in the muscle
are recruited, so that many non-contracting fibres are
usually adjacent to contracting fibres. Coordination by
shear linkages through the endomysium explains how
sarcomere lengths in non-contacting fibres keep in register
with those in adjacent, contracting fibres. This maintains
uniform sarcomere lengths in the muscle. The continuous
meshwork of endomysium that connects adjacent muscle
fibres together, therefore, forms a connecting matrix that
coordinates force transmission between fibres in a fascicle
and keeps fibres in uniform register (Purslow, 2008).
Functional anatomy of the perimysium
Two sizes of fascicles and, therefore, two levels of peri-
mysial structure can be distinguished in cross-sections of
muscle. Small (primary) fascicles or muscle fibre bundles
are delineated by primary perimysium. Groups of primary
fascicles are then organised into larger, secondary fascicles
by secondary perimysium, which tends to be thicker than
primary perimysium. In porcine semitendinosus muscle, the
thicker secondary perimysium is in the order of 10 mm thick
at birth and increases to approach 50 mm in 55 month old
pigs (Fang et al., 1999). The thickness of primary perimy-
sium in cattle muscles ranges from 54.6 m to 133 mm (Brooks
and Savell, 2004).
Both of these perimysial layers form a fenestrated
network that extends across the entire cross-section of the
whole muscle. The perimysium does not form a distinct
sheath that surrounds one fascicle, but rather is a shared
structure lying between two fascicles (Purslow and Trotter,
1994). Nodes form at the junction between perimysial sheets
and the fascicles occupy polygonal ‘‘holes’’ in this network,
in a manner similar to muscle fibres occupying polygonal
‘‘holes’’ in the endomysial network (but at a larger scale). At
the surface of the muscle the perimysium merges and
seamlessly joins with the epimysium (Nishimura et al., 1994).
The perimysial layer separating two fascicles is primarily
comprised of crossed-plies of wavy collagen fibres in
a proteoglycan matrix. In a few muscles (e.g. bovine sem-
itendinosus) there are substantial amounts of elastin fibres
associated with the collagenous network (Rowe, 1981). The
collagen fibre bundles are far larger in diameter than the fine
fibres and fibrils in the endomysium and have a regular
sinusoidal waviness, with all collagen fibre bundles lying
parallel to each other in each ply, and having the same wave
periodicity. In porcine semitendinosus muscle the degree of
waviness has been observed to increase with animal age
415
(Fang et al., 1999). The collagen fibres lie in the plane of the
perimysium, do not run through its thickness, and all the
collagen fibres in each ‘‘ply’’ are parallel to each other and
lie at 55 to the muscle fibre axis at the resting length of the
muscle. This angle changes with muscle length, varying from
around 80 at an extremely short sarcomere length of 1.1 mm
to approximately 20 at a long sarcomere length of 3.9 mm
(Purslow, 1989). Mathematical modelling of the tensile
properties in the plane of this network using fibrous
composites theory (Purslow, 1989), and direct measure-
PREVENTION & REHABILITATIONdFASCIA PHYSIOLOGY
ments of the tensile strength and stiffness of perimysial
sheets dissected from muscle (Lewis and Purslow, 1989;
Purslow, 1999), show that the perimysium is easily deformed
in tension until the collagen fibres have become aligned along
the stretching direction and the waviness in the fibres pulled
out straight. This shows that the perimysium can build up
a high tensile stiffness and carry large loads in tension, but
only at very large extensions well beyond the range of
working lengths in living muscle.
The tensile properties of the perimysium are, therefore,
similar is nature to the endomysium. Both are initially
easily deformed networks that can follow length and
diameter changes imposed by the muscle fibres and fasci-
cles contracting and being lengthened by the action of
antagonistic muscles. It is tempting to extend the analogy
between endomysium and perimysium by proposing that
the perimysium could also act to transmit the forces
generated in fascicles to their adjacent neighbours by
translaminar shear. Although it can be shown that force
transmission by such a mechanism can be invoked in
circumstances of extreme muscle damage or by cutting the
tendinous attachments to some fascicles (Huijing, 2009),
there are two considerations that we can raise that
diminish the likelihood of this mechanism being involved in
living muscle, at least under normal working conditions.
Firstly, considering again that the series-elastic nature of
a shear linkage can be represented as an apparent longi-
tudinal stiffness Eapp and that Eapp given by Eq. (1) above
then even if the perimysium can be up to 50 times thicker
than endomysium, the (L/T )2 term in this equation could
be up to 2500 times smaller for the same length of peri-
mysium than for the endomysium. If the translaminar shear
modulus of the perimysium and endomysium would even be
within an order of magnitude of each other, this means that
thicker perimysium would have a far smaller Eapp, i.e., it
would be far more compliant in shear than the endomy-
sium. This would represent a rather sloppy and inefficient
force transmission pathway.
The second consideration revolves around the observa-
tion that the amounts and structure of endomysium are
relatively constant and only slightly vary between different
muscles, whereas the amounts of perimysium, its thickness,
and the size and shape of primary and secondary muscle
fascicles vary tremendously. The endomysial structures
providing tight shear linkages between adjacent muscle
fibres are reasonably conservative and do not vary so much
from muscle to muscle. So, if the perimysial network
functions similarly, why should its amounts and spatial
arrangement vary so much more?
Schmalbruch (1985) cites a model originally proposed
by Feneis which proposes that the perimysium provides
‘neutral’ connections between adjacent fascicles. These
 416
connections permit fascicles to slide past each other, and
also facilitate shape changes in the muscle during contrac-
tion. All fan-shaped, fusiform, and especially pennate
muscles change shape when contracting, and in order to
accommodate this there must be slippage, or sliding, of some
elements within the muscle (i.e. shear deformations). For
pennate muscles it is easy to formally calculate the shear
strains within the muscles as they contract and the pennation
angles change. In ultrasonic images of human muscles,
‘‘boundaries’’ between fascicles can be seen, and
PREVENTION & REHABILITATION dFASCIA PHYSIOLOGY
measurement of changes in the angle of these during
contraction allows shear strains to be predicted. Shear
strains within working human muscles are substantial and
vary considerably between human muscles such as quadri-
ceps, vastus lateralis and gastrocnemius (Purslow, 2002). If
the endomysium maintains adjacent muscle fibres in tight
shear register, then where can these large and variable shear
strains be accommodated? Simple observations on rigor
muscle that is manipulated to produce internal shear show
that deformations preferentially occur at the boundaries
between fascicles, and that very little shear displacements
occur within a fascicle (Purslow, 1999). If the theory that the
division of muscle into fascicles is to facilitate shear defor-
mations that are necessary for contracting muscle to change
shape is correct, then it seems to offer an explanation of why
the amount and distribution of perimysium changes so very
markedly from muscle to muscle. Thin perimysia surrounding
small fascicles in long strap-like muscles may be associated
with relatively small shear displacements, whereas thicker
perimysial sheets and larger primary fascicles may relate to
larger shear displacements. However, comprehensive data
on the relationship between perimysial thickness, fascicle
size, and the actual distributions of shear strains in working
muscles need to be collected to test this theory.
Control of turnover of IM-ECM as a possible
treatment in muscle injury and repair of
fibrosis
Muscle growth, turnover, and repair necessitate remodelling
of IM-ECM, principally under the control of matrix metal-
loproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs).
MMPs are expressed by muscle cells as well as by fibroblasts in
the IM-ECM (Balcerzak et al., 2001). Adaptation of muscle,
including muscle hypertrophy following exercise training is
known to involve increased expression of a range of MMPs
(Kjaer, 2004). Expression of MMPs is stimulated by mechanical
forces, hormones, and growth factors as well as nutritional
components. Myoblasts express almost as much MMP and total
collagenase activity as fibroblasts in cell culture and tend to
increase this expression more strongly than fibroblasts when
mechanically stimulated by biaxial stretching (Cha and Pur-
slow, unpublished data). Numerically, muscle cells vastly
outnumber fibroblasts within normal muscle tissue. Epineph-
rine (adrenaline) is a general agonist of all types of adrenergic
receptors, and in muscle principally acts to increase glycolysis
via a signalling pathway involving AMP-activated protein
kinase (Shen and Du, 2005). There is also adrenergic control of
protein metabolism in skeletal muscle. Epinephrine acts to
increase calpastatin levels, so reducing protein turnover by
calpains and resulting in net muscle accretion (Navegantes
P.P. Purslow
et al., 2009). Beta-adrenergic agonists (e.g. clenbuterol, rac-
topamine, cimaterol, salbutamol) mimic this effect and
chronic administration of these growth promoters leads to
muscle hypertrophy or amelioration of muscle wasting
(Navegantes et al., 2002). Although some reports associate the
effect of catecholamines on protein metabolism with c-AMP
dependent kinase, Yamaguchi et al. (1997) showed that the
p38 MAPK pathway can be activated by beta-adrenergic
receptors in kidney cells. Expression of MMPs 1 and 13 is acti-
vated by the p38 MAPK pathway in keratinocytes (Johansson
et al., 2000). Recent work in our laboratory (Cha and Purslow,
unpublished data) shows that both skeletal muscle fibroblasts
and myoblasts increase MMP expression in the presence of
epinephrine, but with different time-courses and degrees of
correlation with expression of AMP-activated protein kinase.
Cardiac muscle is obviously different from striated muscle
functionally and structurally, yet there are striking similari-
ties about the organisation and function of ECM structures
between the two muscle types (Purslow, 2008). A change in
the balance between synthesis and degradation of ECM in the
myocardium is a characteristic of many types of heart
failure, including hypertensive heart failure and infarction/
ischemia (Berk et al., 2007; Graham et al., 2008). Banfi et al.
(2005) reported increased plasma levels of MMPs 2&9 in
patients with chronic heart failure and also a significant
correlation between norepinephrine and MMP2 levels.
Cardiac fibroblasts are known to react to both mechanical
stimuli and catecholamines in terms of both proliferation and
expression (Villareal and Kim, 1997), and cardiomyocytes
from chick embryos are known to react to stimulation of the
alpha-adrenergic receptor via noradrenaline by activation of
p38 MAPK (Tsang and Rabkin, 2009). Ongoing studies to
provide fundamental information about the control of
expression of IM-ECM forming cells may have far-reaching
impact on muscle ageing, injury, and repair.
References
Avery, N.C., Bailey, A.J., 2008. Restraining cross-links responsible
for the mechanical properties of collagen fibers; natural and
artificial. In: Fratzl, P. (Ed.), Collagen: Structure and
Mechanics. Springer, NY, pp. 81e110 (Chapter 4).
Bailey, A.J., Paul, R.G., Knott, L., 1998. Mechanisms of maturation
and ageing of collagen. Mechanisms of Ageing and Development
106, 1e56.
Balcerzak, D., Querengesser, L., Dixon, W.T., Baracos, V.E., 2001.
Coordinate expression of matrix-degrading proteinases and
their activators and inhibitors in bovine skeletal muscle. Journal
of Animal Science 79, 94e107.
Banfi, C., Cavalca, V., Veglia, F., Brioschi, M., Barcella, S.,
Mussoni, L., Boccotti, L., Tremoli, E., Biglioli, P., Agostoni, P.,
2005. Neurohormonal activation is associated with increased
levels of plasma matrix metal loproteinase-2 in human heart
failure. European Heart Journal 26, 481e488.
Bendall, J.R., 1967. The elastin content of various muscles of beef
animals. Journal of the. Science of Food & Agriculture 18, 553e558.
Berk, B.C., Fujiwara, K., Lehoux, S., 2007. ECM remodelling in
hypertensive heart disease. Journal of Clinical Investigation
117, 568e575.
Brooks, J.C., Savell, J.W., 2004. Perimysium thickness as an indi-
cator of beef tenderness. Meat Science 67, 329e334.
Bruns, R.R., Gross, J., 1973. High-resolution analysis of the modi-
fied quarter-stagger model of the collagen fibril. Biopolymers
13, 931e994.
Muscle fascia and force transmission
Chiquet, M., Gelman, L., Lutz, R., Maier, S., 2009. From mecha-
notransduction to extracellular matrix gene expression in
fibroblasts. Biochimica Biophysica Acta 1793, 911e920.
Fang, S.H., Nishimura, T., Takahashi, K., 1999. Relationship
between development of intramusclular connective tissue and
toughness of pork during growth of pigs. Journal of Animal
Science 77, 120e130.
Gans, C., Gaunt, A.S., 1991. Muscle architecture in relation to
function. Journal of Biomechanics 24, 53e65.
Graham, H.K., Horn, M., Trafford, A.W., 2008. Extracellular matrix
profiles in the progression to heart failure. Acta Physiologica
194, 3e23.
Huijing, P.A., 2009. Epimuscular myofascial force transmission:
a historical review and implications for new research. Interna-
tional society of biomechanics Muybridge award lecture, Taipei,
2007. Journal of Biomechanics 42, 9e21.
Johansson, N., Alaho, R., Uitto, V.J., Grénman, R.,
Fusenig, N.E., López-Otin, C., Kähäri, V.M., 2000. Expression
of collagenase-3 (MMP-13) and collagenase-1 (MMP-1) by
transformed keratinocytes is dependent on the activity of p38
mitogen-activated protein kinase. Journal of Cell Science 113,
227e235.
Kjaer, M., 2004. Role of extracellular matrix in adaptation of
tendon and skeletal muscle to mechanical loading. Physiological
Reviews 84, 649e698.
Kjær, M., Magnusson, S.P., 2008. Mechanical adaptation and tissue
remodeling. In: Fratzl, P. (Ed.), Collagen: Structure and
Mechanics. Springer, NY, pp. 249e267 (Chapter 9).
Lawson, M.A., Purslow, P.P., 2001. Development of components of
the extracellular matrix, basal lamina and sarcomere in chick
quadriceps and pectoralis muscles. British Poultry Science 42,
315e320.
Lewis, G.J., Purslow, P.P., 1989. The strength and stiffness of
perimysial connective-tissue isolated from cooked beef muscle.
Meat Science 26, 255e269.
Listrat, A., Picard, B., Geay, Y., 1999. Age-related changes and
location of type I, III, IV, V and VI collagens during development
of four foetal skeletal muscles of double muscles and normal
bovine muscles. Tissue and Cell 31, 17e27.
Listrat, A., Lethias, C., Hocquette, J.F., Renand, G., Menissier, F.,
Geay, Y., Picard, B., 2000. Age related changes and location of
types I, III, XII and XIV collagen during development of skeletal
muscles from genetically different animals. Histochemical
Journal 32, 349e356.
Liu, A., Nishimura, T., Takahashi, K., 1995. Structural weakening of
intramuscular connective tissue during post-mortem ageing of
chicken semitendinosus muscle. Meat Science 39, 135e142.
Magid, A., Law, D.J., 1985. Myofibrils bear most of the resting
tension in frog skeletal muscle. Science 230, 1280e1282.
Navegantes, L.C.C., Migliorini, R.H., Kettelhut, I.C., 2002. Adren-
ergic control of protein metabolism in skeletal muscle. Current
Opinion in Clinical Nutrition and Metabolic Care 5, 281e286.
Navegantes, L.C.C., Baviera, A.M., Kettelhut, I.C., 2009. The
inhibitory role of sympathetic nervous system in the Ca2þ-
dependent proteolysis of skeletal muscle. Brazilian Journal of
Medical and Biological Research 42, 21e28.
Nishimura, T., Hattori, A., Takahashi, K., 1994. Ultrastructure of
the intramuscular connective tissue in bovine skeletal muscle.
Acta Anatomica 151, 250e257.
Nishimura, T., Hattori, A., Takahashi, K., 1995. Structural weak-
ening of intramuscular connective tissue during post mortem
ageing of beef. Journal of Animal Science 76, 528e532.
Nishimura, T., Ojima, K., Hattori, A., Takahashi, K., 1997. Devel-
opmental expression of extracellular matrix components in
intramuscular connective tissue of bovine semitendinosus
muscle. Histochemistry and Cell Biology 107, 215e221.
Ohtani, O., Ushiki, T., Taguchi, T., Kikuta, A., 1988. Collagen
fibrillar networks as skeletal frameworks e a demonstration by
View publication stats
417
cell-maceration scanning electron-microscope method.
Archives Of Histology and Cytology 51, 249e261.
Paul, R.G., Bailey, A.J., 1996. Glycation of collagen: the basis of its
central role in the late complications of ageing and diabetes.
International Journal of Biochemistry and Cell Biology 28,
1297e1310.
Podolsky, R.J., 1964. The maximum sarcomere length for contraction
of isolated myofibrils. Journal of Physiology 170, 110e123.
Purslow, P.P., 1989. Strain-induced reorientation of an intramus-
cular connective tissue network: implications for passive
muscle elasticity. Journal of Biomechanics 22, 21e23.
PREVENTION & REHABILITATIONdFASCIA PHYSIOLOGY
Purslow P.P., 1999. The intramuscular connective tissue matrix and
cell-matrix interactions in relation to meat toughness.
Proceedings of the 45th Interantional Congress of Meat Science
and Technology, Yokohama, Japan, pp. 210e219.
Purslow, P.P., 2002. The structure and functional significance of
variations in the connective tissue within muscle. Comparative
Biochemistry and Physiology. A Molecular And Integrative
Physiology 133, 947e966.
Purslow, P.P., 2005. Intramuscular connective tissue and its role in
meat quality. Meat Science 70, 435e447.
Purslow, P.P., 2008. The extracellular matrix of skeletal and
cardiac muscle. In: Fratzl, P. (Ed.), Collagen: Structure and
Mechanics. Springer, NY, pp. 325e358 (Chapter 12).
Purslow, P.P., Duance, V.C., 1990. The structure and function of
intramuscular connective tissue. In: Hukins, D.W.L. (Ed.),
Connective Tissue Matrix, vol. 2. MacMillan, pp. 127e166.
Purslow, P.P., Trotter, J.A., 1994. The morphology and mechanical
properties of endomysium in series-fibred muscles; variations
with muscle length. Journal of Muscle Research and Cell Motility
15, 299e304.
Rowe, R.W.D., 1981. Morphology of perimysial and endomysial
connective tissue in skeletal muscle. Tissue and Cell 13, 681e690.
Schmalbruch, H., 1985. Skeletal Muscle. Springer, Berlin.
Scott, J.E., 1990. Proteoglycan: collagen interactions and subfibrillar
structure in collagen fibrils. Implications in the development and
ageing of connective tissues. Journal of Anatomy 169, 23e35.
Shen, Q.W., Du, M., 2005. Role of AMP-activated protein kinase in
the glycolysis of postmortem muscle. Journal of the Science of
Food and Agriculture 85, 2401e2406.
Swatland, H.J., 1975. Morphology and development of connective
tissue in porcine and bovine muscle. Journal of Animal Science
41, 78e86.
Trotter, J.A., 1993. Functional morphology of force transmission in
skeletal muscle. Acta Anatomica 146, 205e222.
Trotter, J.A., Purslow, P.P., 1992. Functional morphology of the
endomysium in series fibered muscles. Journal of Morphology
212, 109e122.
Trotter, J.A., Richmond, F.J.R., Purslow, P.P., 1995. Functional
morphology and motor control of series fibred muscles. In:
Holloszy, J.O. (Ed.), Exercise and Sports Sciences Reviews, vol.
23. Williams and Watkins, Baltimore, pp. 167e213.
Tsang, M.Y.C., Rabkin, E.W., 2009. p38 Mitogen-activated protein
kinase (MAPK) is activated by noradrenaline and serves a car-
dioprotective role, whereas adrenaline induces p38 MAPK
dephosphorylation. Clinical and Experimental Pharmacology
and Physiology 36, e12ee19.
Velleman, S.G., Liu, X.S., Eggen, K.H., Nestor, K.E., 1999. Devel-
opmental downregulation of proteoglycan synthesis and decorin
expression during turkey embryonic skeletal muscle formation.
Poultry Science 78, 1619e1626.
Villareal, F.J., Kim, N.N., 1997. Regulation of myocardial extra-
cellular matrix components by mechanical and chemical growth
factors. Cardiovascular Pathology 7, 145e151.
Yamaguchi, J., Nagao, M., Kasziro, Y., Itoh, H., 1997. Activation of
p38 mitogen-activated protein kinase by signalling through G
protein-coupled receptors. Journal of Biological Chemistry 272,
27771e27777.