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)