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!
Longitudinal! Pennate! Multipennate!Pennate MultipennateLongitudinalThieme, Atlas of Anatomy, 2007
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.!
Ward et al. (2009) Clin. Orthop. Rel. Res. 467:1074-1082!
High Force Production!
High Excursion!
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!
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!
Lieber, Loren and Fridén (1994) J. Neurophysiol. 71:874-881 .
Diffraction Pattern!
n! = dsin"!
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. !
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? !
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!
Human Muscle Adaptation!
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!
Before After
Clamped!Muscle Fibers!
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
Significant Differences in Bundle Properties!
(n=55 bundles!from 40 pts)!*!
*!
Smith et al. (2011). J. Physiol. (Lond.) 589:2625-2639.
Cerebral Palsy!Typically Developing!
(IHC for Laminin)!
10 µm!
Perimysial cables…!
Satellite Cell: The Muscle “Stem Cell”!
Satellite Cell Sandwich !
Fusion & Elongation!
Migration & Proliferation!
Regenerated Cell!
Fusion & Maturation!
Satellite Cell in Regeneration!
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.
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?!
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.!!
Acknowledgments!
This work was supported by the
NIH, the Department of Veterans Affairs, and the Swedish
Medical Research Council!
http://muscle.ucsd.edu!
Extra Slides to Follow…!
Capillary!
2.5 µm!
Cables!
Gillies, Ellisman and Lieber (unpublished)