Departments of 1 Medicine and 2 Cell Biology, Baylor College of Medicine, Houston, Texas 77030; and 3 Department of Physiological Science, University of California, Los Angeles, California 90095
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ABSTRACT |
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Striated muscle is a linear motor whose properties have been defined in terms of uniaxial structures. The question addressed here is what contribution is made to the properties of this motor by extramyofilament cytoskeletal structures that are not aligned in parallel with the myofilaments. This question arose from observations that transverse loads increase muscle force production in diaphragm but not in the hindlimb muscle, thereby indicating the presence of structures that couple longitudinal and transverse properties of diaphragmatic muscle. Furthermore, we find that the diaphragms of null mutants for the cytoskeletal protein desmin show 1) significant reductions in coupling between the longitudinal and transverse properties, indicating for the first time a role for a specific protein in integrating the three-dimensional mechanical properties of muscle, 2) significant reductions in the stiffness and viscoelasticity of muscle, and 3) significant increases in tetanic force production. Thus desmin serves a complex mechanical function in diaphragm muscle by contributing both to passive stiffness and viscoelasticity and to modulation of active force production in a three-dimensional structural network. Our finding changes the paradigm of force transmission among cells by placing our understanding of the function of the cytoskeleton in the context of the structural and mechanical complexity of muscles.
respiratory muscle mechanics; force transmission; intermediate filaments; mechanics of breathing
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INTRODUCTION |
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SKELETAL MUSCLE FUNCTIONS in a complex, three-dimensional, mechanical environment in which forces can be transmitted across the lateral surfaces of the muscle cell in the transverse plane of the cell, as well as at the ends of the muscle cell, parallel to the longitudinal axis of the cell (2, 18). Biaxial loading is most obviously a feature of the mechanical environment of the diaphragm, in which muscle fibers experience both transverse and longitudinal loads during each respiratory cycle (13). Any elastic sheet that is loaded uniaxially along one direction would have a different length-tension relationship than when the sheet is also loaded in the perpendicular direction. This is true for muscles, and therefore, this complicates the use of uniaxial in vitro properties to analyze in vivo biaxial behavior of the diaphragm muscle. Conducting in vitro physiological experiments under biaxial loading of the diaphragm muscle is therefore critical to the understanding of diaphragm function. Furthermore, the pathways of force transmissions in the diaphragm may be different from those in other skeletal muscles; therefore, specific cytoskeletal proteins and transmembrane proteins may play a unique role in mediating transverse loading of the diaphragm. Our previous findings showed that diaphragmatic muscle is stiffer in the transverse plane (1, 3, 4), which suggests that there are distinct structural components in diaphragm that determine the mechanical characteristics of muscle in the transverse plane. However, the identity of those structures, their mechanical properties, and whether they are functionally coupled to longitudinal structural elements is unknown.
Previous investigations of the structure of active and passive components of the muscle cytoskeleton have led to the thorough description of two functionally and molecularly distinct populations of structural proteins. The first group consists of sarcomeric proteins that are assembled into well-ordered macromolecular assemblies that dominate the active force production by muscle (i.e., sarcomeric actin and myosin) and also others that contribute importantly to the longitudinal passive properties of muscle (e.g., titin and nebulin; see Ref. 22). The second group consists of membrane-associated structural proteins that function in part to transmit forces generated by sarcomeric proteins across the cell membrane (e.g., the integrins and associated structural proteins and the dystrophin complex; see Ref. 19). This latter group is highly concentrated at the ends of the muscle fibers where longitudinally transmitted active and passive forces would be transmitted across the cell membrane. However, these proteins are also enriched in periodic structures, called costameres, at the lateral surface of muscle fibers, which suggests that they function in the transmission or dissipation of forces applied in the transverse plane of the cell.
Although the presence of costameres implies that loading of muscle cells in the transverse plane may be a significant feature of muscle physiology and previous investigations (1, 3, 13) showed that the diaphragm muscle fibers experience transverse loading during normal function, the identity of the transverse structural elements has not been explored. Desmin intermediate filaments provide a prominent candidate for the transverse structural element in muscle in that they are cytoskeletal structures located in the transverse plane of muscle fibers and appear to connect adjacent Z disks in parallel (21). However, desmin intermediate filaments differ from other prominent cytoskeletal structures in muscle because they are oriented in both the transverse and longitudinal planes of the cell (15, 21). This dual orientation suggests the possibility that desmin may not only contribute to the mechanical properties in both the transverse and longitudinal planes, but desmin may also integrate the transverse and longitudinal mechanical systems.
In the present investigation, we used desmin-null mice developed by Milner et al. (14) to test the hypothesis that desmin intermediate filaments integrate the three-dimensional active and passive mechanical properties of the muscle. We tested the contribution of desmin to mechanical properties in muscle that experiences exclusively uniaxial loading along the length of the muscle fibers and in muscle that undergoes biaxial loading. Our findings show that desmin plays a significant role in modulating both the active and passive mechanical functions of muscle, and therefore it contributes to muscle force transmission. The mechanism by which desmin modulates these properties involves coupling the transverse and longitudinal structural systems in muscle.
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METHODS |
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Measurements of passive mechanical properties.
Costal hemidiaphragms from eight 129SV wild-type mice (weight:
20-24 g; age: 8-12 wk old) and eight 129SV desmin-null mice (weight: 18-24 g; age: 8-10 wk old) were used in these
experiments. After anesthetizing the mice and excising the left
hemidiaphragm, muscle was submerged quickly in Krebs-Ringer solution
bubbled with 95% O2-5% CO2 at 25°C. Two
pairs of surgical silk thread markers were sutured along two
neighboring fibers on the abdominal side of the midcostal region. The
biaxial system consists of two orthogonal axes each driven by a stepper
motor to passively lengthen and shorten the muscle. A strain rate of
~0.4 or 1 N · cm2 · s was maintained in
lengthening and shortening of the tissue along both axes; this resulted
in quasi-static loading. The muscle was clamped along both axes, and
force data were collected at a sample rate of 10 Hz using a data
acquisition board (model Lab-PC-1200/AI; National Instruments) and
LabVIEW software (version 5.0). Displacement of the position markers
was recorded with a video recorder (SONY SLV-620HF) and a CCTV type
camera (HV-7200; Hitachi). The recorded video was captured digitally
(Captivator PC, by VideoLogic) at a sample rate of 1 Hz and was
analyzed using Image Tool (version 2.0). Two-dimensional coordinates
were obtained for each marker, and displacement was computed using
MATLAB (version 5.2) software. To compute the length-tension
relationship, muscles were passively lengthened and shortened along the
muscle fibers as well as transverse to the muscle fibers. Muscles were
passively lengthened from unstressed length (~0.7 optimal length) to
~1.25-1.35 optimal muscle length (or the length at which twitch
force is maximal). Muscles were then passively shortened until passive
force was negligible. Tension in Newtons per centimeter was computed by
dividing muscle force in Newtons by the clamp width in centimeters.
With the use of MATLAB (version 5.2) software, the extensibility of
diaphragm muscle during passive lengthening was assessed by computing
the extension ratio
, the ratio of muscle length at the deformed state to muscle length at the unstressed state.
Measurements of contractile properties. Muscles from eight wild-type 129SV mice (weight: 19.5 ± 4.1 g; age: 67.3 ± 8.8 days) and nine desmin-null 129SV mice (weight: 20.3 ± 2.2 g; age: 80.3 ± 8.5 days) were used. Upon anesthetizing the animals, biceps femoris muscle was excised and placed in a muscle bath with continuously circulating 25°C oxygenated 95% O2-5% CO2 Krebs-Ringer solution. Muscle was positioned between two stainless steel mesh electrodes, and optimal length was determined by twitch responses (0.1-ms stimulus duration, supramaximal voltage). At optimal length, we tetanically stimulated the muscle at 100 and 10 Hz with 120 s recovery (supramaximal voltage, 0.5-ms pulses; and tetanic train duration of 500 ms). Tetanic stimulations were repeated in the presence of a transverse load of ~0.01 N. Subsequently, the diaphragm was excised and stimulated at 100 and 10 Hz preceded by twitches. Muscle stimulations were executed in the presence of a transverse to fiber load of 0, 0.01, and 0.02 N with 120 s recovery, and the sequence was repeated two more times. All data were acquired at 300 Hz.
Thickness measurements. Frozen sections were cut at 10-µm thickness through diaphragm and biceps femoris muscles along the axis of loading. Sections were then observed by Nomarski optics, and the clamp-to-clamp distance for the tissue in each section and the total area of tissue in each section was measured using a digital imaging system (Bioquant, Nashville, TN). Mean thickness of the muscle along the axis of loading was then calculated by dividing the tissue area by the clamp-to-clamp distance.
Stress-relaxation assays.
With the use of the same muscles from the passive length-tension
protocol, stress-relaxation data were obtained by holding the muscle
length constant after passively loading the muscle to ~0.25 of peak
active stress. Muscle tension was allowed to relax asymptotically until
it essentially reached a plateau. Three passive stretching maneuvers
were executed: uniaxial along the fibers, uniaxial transverse to the
fibers, and a biaxial loading. In the biaxial protocol, a 0.01 N was
applied in the transverse fiber direction, and then muscle was
stretched to a length that is equivalent to muscle optimal
length. We then fit exponential equations based on Kelvin's
mechanical model of viscoelastic material properties to the four sets
of stretch-relaxation curves. Kelvin's model, also commonly called the
standard linear model, describes the muscle fiber as a parallel
combination of a dashpot with coefficient of viscosity,
1, and a linear spring with spring constant,
µl, with a second linear spring with spring constant
µo (9). The relaxation function based on
this model has the form F = ER [1
(1
/
)
e
t/
], where F is the
relaxation force, t is time, ER is
the relaxed elastic modulus,
is the relaxation time
for constant strain, and
is the relaxation time for
constant stress. After obtaining the three constants
ER,
, and
,
we calculated the viscoelastic coefficients
1,
µ1, and µo based on the force-displacement relationships of the model. The ratio
/µ is a relaxation time, and
it characterizes the rate of relaxation of the dashpot.
Electron microscopy. At the end of experimental treatments, muscles were fixed in 1.4% glutaraldehyde in 0.20 M sodium cacodylate buffer, pH 7.2, on ice. After 30 min, muscles were rinsed in cacodylate buffer and dissected into blocks containing the muscle. Samples were postfixed in 1% OsO4 and rinsed in buffer. Samples were then dehydrated in graded ethanol concentrations and embedded in epoxy resin. Sections of 0.5-µm thickness were cut in the longitudinal or transverse midbelly plane of each muscle. Samples free of preparation artifacts and detectable by light microscopy were then thin sectioned for electron microscopy. Thin sections at 60-nm thickness were stained with uranyl acetate and lead citrate and were observed using a Zeiss EM10AG transmission electron microscope.
Western analysis. Entire diaphragms or biceps femoris muscles from control mice were prepared by homogenizing samples in 80 mM Tris · HCl, pH 6.8, 0.1 M dithiothreitol, 70 mM SDS, and 1.0 mM glycerol. The homogenates were then heated to 100°C for 1 min and centrifuged to remove insoluble material. Protein concentration in the supernatant was determined by measuring absorbance at 280 nm. Samples containing 50 µg of total protein were separated on 12% acrylamide gels according to Laemmli (12). Proteins were then electrophoretically transferred to nitrocellulose membranes (5). After transfer, the uniformity of protein loading and efficiency of transfer were assessed by staining membranes with Ponceau S (Sigma). Nonspecific binding to proteins in the nitrocellulose membranes was blocked by immersing the membranes in buffer containing 0.5% Tween 20, 0.2% gelatin, and 3.0% dry milk (blocking buffer) for at least 1 h at room temperature. Membranes were probed with polyclonal anti-desmin (Sigma, St. Louis, MO) for 90 min at room temperature. Membranes were overlaid with alkaline phosphatase-conjugated anti-rabbit IgG (Sigma) for 1 h at room temperature. The membranes were washed six times for 10 min in 0.5% Tween 20, 0.2% gelatin, and 0.3% dry milk and then were developed using nitroblue tetrazolium and bromochloroindolyl phosphate. The relative concentration of desmin in each sample was determined by scanning densitometry (Alpha Innotec, San Leandro, CA).
Statistical analysis. Statistical differences between groups were assessed by ANOVA with the use of the SAS Procedure "Mixed" Program. The model was a two-factor fixed- or random-effects model for two groups (desmin-null vs. controls) and two treatments (uniaxial vs. biaxial). A 0.05 level of significance was chosen a priori.
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RESULTS |
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Desmin increases stiffness in the transverse plane of diaphragm
muscle.
We first tested the hypothesis that the diaphragm that experiences
transverse loading in vivo would display structural, mechanical, and
molecular specialization that reflects its specialized mechanical environment. Data in Fig. 1 show that the
length-tension relationship of normal diaphragm is shifted to the right
compared with the length-tension curve in the transverse plane, that
is, the normal diaphragm muscle is anisotropic with a greater
extensibility in the direction of the muscle fibers than transverse to
the fibers. In contrast, in the desmin-null diaphragm, the
length-tension curve along the fibers is essentially superimposed on
that in the transverse plane. Using all diaphragms from desmin-null and control mice, we computed the extension ratio, , at tension of ~0.1 N/cm along the fiber direction and found
to be statistically similar in the desmin-null and normal mice diaphragms
(Des
/
:
= 1.18 ± 0.05;
Des+/+:
= 1.17 ± 0.03; P < 0.74). Data in Fig. 1 show that the length-tension transverse to the
fibers is shifted to the right in the desmin-null diaphragm compared
with that of the normal diaphragm. Using all diaphragms from
desmin-null and control mice, we computed the extension ratio at ~0.1
N/cm applied in the direction transverse to muscle fibers and found
that
was significantly greater in the desmin-null mice than in
control mice (Des
/
:
= 1.23 ± 0.04, Des+/+:
= 1.06 ± 0.03; P < 0.001). These data demonstrate that the diaphragm in the transverse
plane has significantly more extensible muscle in the desmin-null mouse
than in the normal mouse.
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Desmin couples the transverse and longitudinal mechanical
properties of diaphragm muscle.
Further experimentation provided evidence that structures contributing
to transverse stiffness in normal diaphragm muscle are mechanically
coupled to longitudinal structural elements. Transverse loads increased
the twitch stress in the diaphragm by ~28% (Des+/+:
17.6 ± 1.3 vs. 13.8 ± 1.3 N/cm2;
Des/
: 17.9 ± 0.6 vs. 22.1 ± 0.8 N/cm2). Furthermore, transverse passive loads increased
maximal tetanic stress by ~45% as shown in Fig.
2. It is noteworthy that tetanic stresses
were reproducible after recovery. Electron microscopic observations
provided structural correlation for the mechanical evidence of coupling
between transverse and longitudinal mechanical elements. Both normal
and desmin-null mouse diaphragms placed under transverse loads showed
sites where the sarcolemma of the loaded muscle fibers protruded
laterally, reflecting the effect of a transverse load placed on the
fiber. However, normal diaphragm muscle but not biceps femoris showed
hypercontraction of the sarcomeres adjacent to these sites, while the
lengths of sarcomeres of desmin-null muscle at sites of transverse
loading did not differ from sarcomere lengths elsewhere in the muscle
fiber (Fig. 3). In the diaphragm muscle,
the maximal longitudinal compressive sarcomere strain in normal muscles
was ~75% in the zones of shortened myofibrils in the transversely
loaded controls. In an identically transversely loaded sample of
desmin-null muscle, however, there was ~0% longitudinal sarcomere
strain, that is, sarcomere length in the loaded muscle was about the
same as relaxed sarcomere length. These measurements were calibrated
relative to the thick filament length in fixed, embedded, and sectioned
tissue. Thick filament length was set at 1.0 µm. For example,
for normal muscle, the length of the fixed shortened sarcomeres was
25% of the length of the fixed relaxed sarcomeres; therefore, no
further adjustment for differential shrinkage should be necessary. The
absence of desmin reduced the mechanical coupling between transverse
loading and either tetanic or twitch stress production. Our data do not
exclude residual coupling in the absence of desmin, suggesting the
presence of additional, unknown structural elements that link
longitudinal and transverse mechanical properties. However, no
sarcomeric shortening was observed in desmin-null diaphragm muscles
subjected to transverse loading, which provides further support for a
major role of desmin in coupling longitudinal and transverse structural
elements.
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Desmin concentration is greater in the diaphragm than hindlimb
muscles.
Western analysis followed by densitometry of immunoblots shows that
diaphragm muscle contains 38% more desmin than the biceps femoris
muscle (Fig. 5; biceps femoris desmin
normalized at 1.00 arbitrary unit, SE = 0.01; diaphragm desmin
concentration = 1.38 units; SE = 0.01; n = 3;
P < 0.05; Mann-Whitney) and suggests that this
difference in desmin concentration may relate to the difference in
detectable coupling between transverse and longitudinal mechanical
properties of diaphragm and hindlimb muscle.
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Desmin increases diaphragm stress relaxation and decreases
diaphragm muscle force production.
Stress-relaxation assays showed that, when a static load was applied to
diaphragm muscle, the decrease in muscle stress over time was reduced
significantly in desmin-null diaphragms (Fig. 6). Stress relaxation in the normal
diaphragm is greater than in the desmin-null diaphragm. After uniaxial
loading in the direction along the fibers, the values of the relaxed
elastic modulus, ER, for the desmin-null was
greater than for control diaphragms (Des/
:
ER = 0.73 ± 0.01; Des+/+:
ER = 0.63 ± 0.04; P < 0.004). After uniaxial loading in the direction transverse to
fibers, these ER values were 0.84 ± 0.001 for Des
/
and 0.73 ± 0.045 for Des+/+
(P < 0.012). The effect of desmin deficiency on the
stress relaxation curve is pronounced in both longitudinal and
transverse planes. Furthermore, the effect of desmin deficiency was
also pronounced after a biaxial load (biaxial Des
/
:
ER = 0.81 ± 0.05 and
Des+/+: ER = 0.64 ± 0.07;
P < 0.001). Thus desmin contributes to muscle viscosity in diaphragms experiencing loading along the muscle longitudinal axis, loaded only in the transverse plane, or subjected to
biaxial loading, but the effect is most prominent during biaxial loading. These findings indicate that desmin intermediate filaments may
contribute to the dissipation of mechanical energy during passive
loading of diaphragms during normal breathing.
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DISCUSSION |
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A previous discovery demonstrated that desmin intermediate filaments were oriented in both the transverse and longitudinal planes of the muscle cell and appeared to join Z disks in series in a single myofibril and in parallel in adjacent myofibrils (15, 21). This discovery led to speculations that desmin could function as a template for sarcomere assembly (10) or as a structural element conferring stiffness to muscle fibers in both the transverse and longitudinal planes (15, 20, 21). However, the generation of desmin-null mutant mice capable of forming apparently normal sarcomeres and myofibrils (14) disproved the view that desmin was essential for sarcomeric organization. Our data substantiate the expectation that desmin increases passive stiffness of diaphragm muscle but show that this contribution to stiffness exists primarily in the transverse plane of the diaphragm muscle. More importantly, the results support two distinct, prominent roles of desmin in skeletal muscle. First, desmin couples transverse and longitudinal structural elements in the muscle cytoskeleton, and second, it acts as a viscous element that dissipates mechanical energy in both the longitudinal and transverse planes of the muscle.
The contribution of desmin to muscle viscoelasticity in stress relaxation experiments and to active force dissipation in contracting muscle may reflect a common energy-dissipating feature of the desmin cytoskeleton. Although the present findings do not allow identification of the energy-dissipative structure, knowledge of the structure and organization of intermediate filaments (11, 17) indicates several sites as potential viscous, force-dissipating elements. First, it is feasible that elongation of the coiled-coil domain of desmin could contribute to muscle viscosity and that the intermediate filaments would increase muscle stiffness after elongation of the coiled-coil domains was complete. Alternatively, electron microscopic observations of desmin intermediate filament organization in muscle show that the filaments are not aligned perfectly in the transverse or longitudinal planes. Thus the initial viscous response of the desmin cytoskeletal system may reflect intermediate filament reorientation, after which the aligned filaments would increase muscle stiffness.
Identification of a structural protein involved in coupling the mechanical behavior of muscle cells in the transverse and longitudinal planes is unprecedented and may have substantial significance in the understanding of the mechanisms of force transmission in skeletal muscle in vivo. For example, the finding that biaxial loading of muscle can increase twitch and tetanic stress production indicates that the determinants of muscle contractility in vivo are more complex than predicted by excised muscle in vitro preparations in which the muscle is subjected exclusively to longitudinal loading (6, 7, 16). Although at first view it may appear contradictory that the presence of desmin reduces twitch and tetanic stresses in the diaphragm, the increase in twitch and tetanic stresses that result from biaxial loading of muscle requires the presence of desmin. However, the two sets of findings are compatible in more than one hypothetical model. For example, if the viscous element in the desmin cytoskeletal system resides primarily in the coiled-coil domain of the molecule, the application of biaxial loading could preload the viscous element so that it would not dissipate force during muscle contraction. Alternatively, if the viscosity is attributable to energy dissipation during realignment of the desmin intermediate filaments, application of transverse loads could cause realignment before contraction and thereby reduce energy losses.
The ability to amplify twitch stress production by 28% through the application of transverse loads to muscle indicates a new level of molecular specialization of muscle that can have important implications for muscle function. By comparison, differences in muscle fiber type permit variability in maximum twitch force production by ~80% and yield no significant change in tetanic stress production (8). In addition, changes in muscle fiber type result from muscle adaptations controlled at the transcriptional and translational levels. The ability of muscle to modulate maximum stress production by the application of transverse passive stress is a more flexible system for the modulation of twitch stress production. Such a modulation does not require regulation through the relatively slow processes that regulate protein synthesis, and it is a regulatory mechanism that is under voluntary control. The extent to which this newly identified mechanism for amplifying muscle stress is exploited through physiologically distinct muscles and various species remains to be explored.
In summary, our data demonstrate that passive transverse stress alters the production of both maximal and submaximal contractile properties in normal diaphragm, and this effect is absent in the desmin-null muscles. Furthermore, the diaphragm in the transverse plane is significantly more extensible in the desmin-null mouse than in the normal mouse. In addition, desmin intermediate filaments may contribute to the dissipation of mechanical energy of the diaphragm during normal breathing. We conclude that both physiological and structural data suggest that the mechanism of force transmission is altered by desmin. In particular, desmin contributes to force transmission as an integrator of the three-dimensional mechanical properties of the diaphragm.
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ACKNOWLEDGEMENTS |
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The authors thank Drs. D. Milner and Deshen Zhu for technical assistance. They also thank Drs. G. Cooper, M. P. Sheetz, and G. Gundersen for insightful and valuable comments.
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FOOTNOTES |
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This investigation was supported by National Institutes of Health Grants HL-63134, AR-39617, and AR-40343.
A. M. Boriek, Suite 520B, Pulmonary and Critical Care Medicine, Dept. of Medicine, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030 (E-mail address: boriek{at}bcm.tmc.edu).
The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
Received 23 March 2000; accepted in final form 14 August 2000.
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REFERENCES |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
1.
Boriek, AM,
Kelly NG,
Rodarte JR,
and
Wilson TA.
Biaxial constitutive relations for the canine diaphragm.
J Appl Physiol
89:
2187-2190,
2000
2.
Boriek, AM,
Miller CC,
and
Rodarte JR.
Muscle fiber architecture of the dog diaphragm.
J Appl Physiol
84:
318-326,
1998
3.
Boriek, AM,
Rodarte JR,
and
Reid MB.
Shape and tension distribution of the passive rat diaphragm.
Am J Physiol Regulatory Integrative Comp Physiol
280:
33-41,
2001.
4.
Boriek, AM,
Wilson TA,
and
Rodarte JR.
Displacement and strains in the costal diaphragm of the dog.
J Appl Physiol
76:
223-229,
1994
5.
Burnette, WN.
"Western blotting": electrophoretic transfer of proteins from sodium dodecyl sulfate-polyacrylamide gels to unmodified nitrocellulose and radiographic detection with antibody and radioiodinated protein A.
Anal Biochem
112:
195-203,
1981[ISI][Medline].
6.
Farkas, GA,
and
Rochester DF.
Functional characteristics of canine costal and.
J Appl Physiol
65:
2253-2260,
1988
7.
Faulkner, JA,
Maxwell LC,
Ruff GL,
and
White TP.
The diaphragm as a muscle. Contractile properties.
Am Rev Respir Dis
119:
89-92,
1979[ISI][Medline].
8.
Fitts, RH,
and
Widrick JJ.
Muscle mechanics: adaptations with exercise-training.
Exerc Sport Sci Rev
24:
427-473,
1996[Medline].
9.
Fung, YC.
Biomechanics: Mechanical Properties of Living Tissues. New York: Springer-Verlag, 1993, p. 41-48.
10.
Furst, DO,
Osborn M,
and
Weber K.
Myogenesis in the mouse embryo: differential onset of expression of myogenic proteins and the involvement of titin in myofibril assembly.
J Cell Biol
109:
517-527,
1989[Abstract].
11.
Herrmann, H,
and
Aebi U.
Structure, assembly, and dynamics of intermediate filaments.
Subcell Biochem
31:
319-362,
1998[Medline].
12.
Laemmli, UK.
Cleavage of structural proteins during the assembly of the head of bacteriophage T4.
Nature
227:
680-685,
1970[ISI][Medline].
13.
Margulies, SS,
Lei GT,
Farkas GA,
and
Rodarte JR.
Finite element analysis of stress in the canine diaphragm.
J Appl Physiol
76:
2070-2075,
1994
14.
Milner, DJ,
Weitzer G,
Tran D,
Bradley A,
and
Capetanaki Y.
Disruption of muscle architecture and myocardial degeneration in mice lacking desmin.
J Cell Biol
134:
1255-1270,
1996[Abstract].
15.
Price, MG,
and
Sanger JW.
Intermediate filaments in striated muscle.
Cell Muscle Motil
3:
1-39,
1983[Medline].
16.
Sant'Ambrogio, G,
and
Saito F.
Contractile properties of the diaphragm in some mammals.
Respir Physiol
70:
349-357,
1970.
17.
Shoeman, RL,
and
Traub P.
Assembly of intermediate filaments.
Bioessays
15:
605-611,
1993[ISI][Medline].
18.
Street, SF.
Lateral transmission of tension in frog myofibers: a myofibrillar network and transverse cytoskeletal connections are possible transmitters.
J Cell Physiol
114:
346-364,
1983[ISI][Medline].
19.
Tidball, JG.
Force transmission across muscle cell membranes.
J Biomech
24:
43-52,
1991[ISI][Medline].
20.
Tidball, JG.
Desmin at myotendinous junctions.
Exp Cell Res
199:
206-212,
1992[ISI][Medline].
21.
Tokuyasu, KT,
Dutton AH,
and
Singer SJ.
Immunoelectron microscopic studies of desmin (skeleton) localization and intermediate filament organization in chicken skeletal muscle.
J Cell Biol
96:
1727-1735,
1983[Abstract].
22.
Trinick, J.
Elastic filaments and giant proteins in muscle.
Curr Opin Cell Biol
3:
112-119,
1991[Medline].