richard l. lieber
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Richard L. Lieber!Departments of Bioengineering and Orthopaedics!University of California, San Diego!Veterans Affairs Medical Center!La Jolla, California!
Intraoperative measurement and biomechanical studies
of human muscle!
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Longitudinal! Pennate! Multipennate!Pennate MultipennateLongitudinalThieme, Atlas of Anatomy, 2007
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Significance of Muscle Architecture!
•" Muscle force proportional to the physiological CSA!Gans (1982) Ex. Science Sport Rev. 10:160-207.!Powell et al. (1984) J. Appl. Physiol. 57:1715-1721.!
•" Muscle excursion is proportional to fiber length!Bodine et al. (1982) J. Neurophysiol. 48:192-201.!Winters et al. (2011) J. Morphol. 44:109-115.!
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Ward et al. (2009) Clin. Orthop. Rel. Res. 467:1074-1082!
High Force Production!
High Excursion!
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Sarcomere length-tension relationship!
4.0!3.5!3.0!2.5!2.0!1.5!1.0!0.5!0.50!
20!
40!
60!
80!
100!
Sarcomere Length (µm) !
Active! Passive!
100
Rel
ativ
e M
uscl
e Te
nsio
n!
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Physiological Operating Range?!
4.0!3.5!3.0!2.5!2.0!1.5!1.0!0.5!0.50!
20!
40!
60!
80!
100!
Sarcomere Length (µm) !
?!?!
?!
?!
?!
100
Perc
ent M
axim
um T
ensi
on!
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Lieber, Loren and Fridén (1994) J. Neurophysiol. 71:874-881 .
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Diffraction Pattern!
n! = dsin"!
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Sarcomere Length vs. Joint Angle!
100!75!50!25!0!-25!-50!-75!-100!-1002.0!
2.5!
3.0!
3.5!
4.0!
4.5!
Wrist Joint Angle (°)!
Sarc
omer
e Le
ngth
(µm
)!
Lieber, Loren and Fridén (1994). J. Neurophysiol. 70:874-881. !
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Intraoperative FCU Measurements!
•" Spastic FCU wrist flexion contractures (n=9)!
•" “Normal” FCU muscles with wrist in full flexion (n=12, radial nerve palsy)!
Spastic FCU wrist flexion contractures
“Normal” FCU muscles with wrist in full
Prediction? !
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Sarcomere Length Comparison!
2.2!2.4!2.6!2.8!3.0!3.2!3.4!3.6!
Spastic! Normal!
3.54±0.4!
2.4±0.3!Sarc
omer
e Le
ngth
(µm
)!
Lieber and Fridén (2002). Muscle & Nerve 25:265-270
4.0!3.5!3.0!2.5!2.0!1.5!1.0!0.5!0.50!
20!
40!
60!
80!
100!
Sarcomere Length (µm) !
100
Rel
ativ
e M
uscl
e Te
nsio
n! 2.4!
3.5!
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Human Muscle Adaptation!
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Boakes, Foran, Ward and Lieber (2006). Clin. Orthop. Rel. Res. 456:250-253!
Number = 9.1cm2.64µm
= 25,000
Before!
Number = 18.2cm3.11µm
= 58,650
After!
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Before After
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Clamped!Muscle Fibers!
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Measuring fibers and tissues…!
To Force!Tranducer! To Motor!
Fiber Segment!10-0 Suture!
0.5 mm!
Lieber et al. (2003). Muscle & Nerve 28:464-471
Fridén and Lieber (2003). Muscle & Nerve 27:157-164
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Significant Differences in Bundle Properties!
(n=55 bundles!from 40 pts)!*!
*!
Smith et al. (2011). J. Physiol. (Lond.) 589:2625-2639.
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Cerebral Palsy!Typically Developing!
(IHC for Laminin)!
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10 µm!
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Perimysial cables…!
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Satellite Cell: The Muscle “Stem Cell”!
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Satellite Cell Sandwich !
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Fusion & Elongation!
Migration & Proliferation!
Regenerated Cell!
Fusion & Maturation!
Satellite Cell in Regeneration!
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Which Cells are the “Players?”!
*!*
Satellite Endothelial Inflammatory0
5
10
15
20
25
Perc
ent E
ach
Cell T
ype
Cerebral PalsyTypically Developing
Cell Cell Cell
*
Implications…!• Growth!• Repair!• Regeneration!• Hypertrophy!• Therapy!
Smith, Chambers & Lieber. (2013). Dev. Med. Child Neurol. 55:264-270.
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Summary!
•" Main functional properties of muscle are determined by architecture.!
•" Architecture then “tuned” according to sarcomere length operating range.!
•" Architectural properties are “plastic”!Cerebral Palsy!Limb Lengthing!Injury/Repair?!
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Summary (cont.)!
•" The main workhorse of muscle repair is the satellite cell:!Numbers? !Effect of Age?!
Types? ! !Effect of Regeneration?!
•" Important to apply these fundamental concepts to the problems of sports injury and treatment.!!
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Acknowledgments!
This work was supported by the
NIH, the Department of Veterans Affairs, and the Swedish
Medical Research Council!
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http://muscle.ucsd.edu!
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Extra Slides to Follow…!
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Capillary!
2.5 µm!
Cables!
Gillies, Ellisman and Lieber (unpublished)
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