Richard L. Lieber
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- Muscle architecture, including fiber length and physiological cross-sectional area, determines its main functional properties of force production and excursion. Architecture is tuned by the sarcomere length operating range. - Muscle architectural properties are plastic and can adapt through processes like limb lengthening or cerebral palsy. This adaptation occurs through changes in fiber length and number. - Satellite cells are the main cell type responsible for muscle repair, regeneration, growth, and hypertrophy. Their numbers and types may be affected by factors like age and the extent of regeneration required. - Understanding muscle architecture and adaptation at the cellular level can help address problems in sports medicine and develop new injury treatments.
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Richard L. Lieber
- 1. Intraoperative measurement and biomechanical studies of human muscle ! Richard L. Lieber! Departments of Bioengineering and Orthopaedics! University of California, San Diego! Veterans Affairs Medical Center! La Jolla, California!
- 3. Longitudinal Longitudinal! Pennate Pennate! Multipennate Multipennate! Thieme, Atlas of Anatomy, 2007
- 4. 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.!
- 5. High Force Production! High Excursion ! Ward et al. (2009) Clin. Orthop. Rel. Res. 467:1074-1082!
- 6. Relative Muscle Tension! Sarcomere length-tension relationship ! 100 100! Active! 80! Passive! 60! 40! 20! 0! 0.5 0.5! 1.0! 1.5! 2.0! 2.5! 3.0! Sarcomere Length (µm) ! 3.5! 4.0!
- 7. Percent Maximum Tension! Physiological Operating Range? ! ?! 100 100! ?! 80! ?! 60! ?! 40! ?! 20! 0! 0.5 0.5! 1.0! 1.5! 2.0! 2.5! 3.0! Sarcomere Length (µm) ! 3.5! 4.0!
- 8. Lieber, Loren and Fridén (1994) J. Neurophysiol. 71:874-881 .
- 9. n! = dsin"! Diffraction Pattern!
- 11. Sarcomere Length (µm)! Sarcomere Length vs. Joint Angle ! 4.5! 4.0! 3.5! 3.0! 2.5! 2.0! -100 -100! -75! -50! -25! 0! 25! 50! 75! Wrist Joint Angle (°)! Lieber, Loren and Fridén (1994). J. Neurophysiol. 70:874-881. ! 100!
- 12. Intraoperative FCU Measurements ! •" Spastic FCU wrist flexion contractures (n=9)! •" “Normal” FCU muscles with wrist in full flexion (n=12, radial nerve palsy)! Prediction? !
- 13. 3.6! 3.4! 3.54±0.4! 3.2! 3.0! 2.8! 100 100! 2.4! 2.4! 80! 60! 40! 20! 0! 0.5 0.5! 2.6! 2.2! Relative Muscle Tension! Sarcomere Length (µm)! Sarcomere Length Comparison ! 3.5! 1.0! 1.5! 2.0! 2.5! 3.0! Sarcomere Length (µm) ! 3.5! 2.4±0.3! Spastic! Normal! Lieber and Fridén (2002). Muscle & Nerve 25:265-270 4.0!
- 15. Before! After ! 9.1cm Number = = 25,000 2.64 µ m 18.2cm Number = = 58, 650 3.11µ m Boakes, Foran, Ward and Lieber (2006). Clin. Orthop. Rel. Res. 456:250-253!
- 16. Before After
- 18. Measuring fibers and tissues…! Fridén and Lieber (2003). Muscle & Nerve 27:157-164 To Force! Tranducer! To Motor! Fiber Segment! 10-0 Suture! 0.5 mm! Lieber et al. (2003). Muscle & Nerve 28:464-471
- 19. Significant Differences in Bundle Properties ! *! *! Smith et al. (2011). J. Physiol. (Lond.) 589:2625-2639. (n=55 bundles! from 40 pts)!
- 20. Typically Developing! Cerebral Palsy! (IHC for Laminin)!
- 21. 10 µm!
- 23. Satellite Cell: The Muscle “Stem Cell” !
- 24. Satellite Cell Sandwich !
- 25. Satellite Cell in Regeneration ! Migration Maturation! Fusion & & Proliferation! Regenerated Cell! Fusion & Elongation!
- 26. Which Cells are the “Players?” ! Percent Each Cell Type 25 Implications…! • Growth! • Repair! • Regeneration! • Hypertrophy! • Therapy! Cerebral Palsy Typically Developing 20 15 10 * * *! 5 0 Satellite Cell Endothelial Cell Inflammatory Cell Smith, Chambers & Lieber. (2013). Dev. Med. Child Neurol. 55:264-270.
- 27. 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?!
- 28. Summary (cont.) ! •" The main workhorse of muscle repair is the satellite cell:! Numbers? Types? ! •" !Effect of Age?! !Effect of Regeneration?! Important to apply these fundamental concepts to the problems of sports injury and treatment.! !
- 29. Acknowledgments ! This work was supported by the NIH, the Department of Veterans Affairs, and the Swedish Medical Research Council !
- 31. Extra Slides to Follow… !
- 32. Capillary! Cables! 2.5 µm! Gillies, Ellisman and Lieber (unpublished)