Biophysical Reviews

, Volume 3, Issue 4, pp 199–207 | Cite as

Mechanisms of residual force enhancement in skeletal muscle: insights from experiments and mathematical models



A skeletal muscle that is stretched while contracting will produce more force at steady state than if it is stretched passively and then stimulated to contract. This phenomenon is known as residual force enhancement and has been widely studied since its description more than 60 years ago. The idea that the mechanical properties of a muscle are governed not just by its present length but also by its length at earlier time points has far reaching implications since muscles stretch and shorten routinely in normal use. In this review, we present the experimental and theoretical advances that have been made toward understanding the mechanisms that underlie residual force enhancement. In the past 10 years, experiments and models have focused on essentially three candidate mechanisms for residual force enhancement: (half-) sarcomere inhomogeneity, activity of so-called ‘passive’ mechanical elements in the sarcomere (titin), and the intrinsic properties of myosin crossbridges. Evidence, both computational and experimental, is accumulating for each of these mechanisms such that a final description of the phenomenon seems attainable in the near future. We conclude that computational models that incorporate more than one putative mechanism may ultimately facilitate reconciliation of the growing number of ideas and experimental data in this field.


Residual force enhancement Computational modeling Skeletal muscle Half-sarcomeres 


  1. Abbott B, Aubert X (1952) The force exerted by active striated muscle during and after change of length. J Physiol 117(1):77–86PubMedGoogle Scholar
  2. Bagni MA, Cecchi G, Colomo F, Garzella P (1994) Development of stiffness precedes cross-bridge attachment during the early tension rise in single frog muscle fibres. J Physiol 481(Pt 2):273–278PubMedGoogle Scholar
  3. Bagni MA, Cecchi G, Colombini B, Colomo F (2002) A non-cross-bridge stiffness in activated frog muscle fibers. Biophys J 82(6):3118–3127. doi: 10.1016/S0006-3495(02)75653-1 PubMedCrossRefGoogle Scholar
  4. Bagni MA, Colombini B, Geiger P, Berlinguer Palmini R, Cecchi G (2004) Non-cross-bridge calcium-dependent stiffness in frog muscle fibers. Am J Physiol Cell Physiol 286(6):C1353–1357. doi: 10.1152/ajpcell.00493.2003 PubMedCrossRefGoogle Scholar
  5. Bianco P, Nagy A, Kengyel A, Szatmari D, Martonfalvi Z, Huber T, Kellermayer MS (2007) Interaction forces between F-actin and titin PEVK domain measured with optical tweezers. Biophys J 93(6):2102–2109. doi: 10.1529/biophysj.107.106153 PubMedCrossRefGoogle Scholar
  6. Brown LM, Hill L (1991) Some observations on variations in filament overlap in tetanized muscle fibres and fibres stretched during a tetanus, detected in the electron microscope after rapid fixation. J Muscle Res Cell Motil 12(2):171–182PubMedCrossRefGoogle Scholar
  7. Brunello E, Reconditi M, Elangovan R, Linari M, Sun YB, Narayanan T, Panine P, Piazzesi G, Irving M, Lombardi V (2007) Skeletal muscle resists stretch by rapid binding of the second motor domain of myosin to actin. Proc Natl Acad Sci USA 104(50):20114–20119. doi: 10.1073/pnas.0707626104 PubMedCrossRefGoogle Scholar
  8. Campbell KS (2009) Interactions between connected half-sarcomeres produce emergent mechanical behavior in a mathematical model of muscle. PLoS Comput Biol 5(11):e1000560. doi: 10.1371/journal.pcbi.1000560 PubMedCrossRefGoogle Scholar
  9. Campbell SG, Hatfield PC, Campbell KS (2011) A Mathematical Model of Muscle Containing Heterogeneous Half-sarcomeres Exhibits Residual Force Enhancement. PLoS Comput Biol 7(9):e1002156. doi: 10.1371/journal.pcbi.1002156 PubMedCrossRefGoogle Scholar
  10. Colombini B, Nocella M, Benelli G, Cecchi G, Bagni MA (2007) Crossbridge properties during force enhancement by slow stretching in single intact frog muscle fibres. J Physiol 585(Pt 2):607–615. doi: 10.1113/jphysiol.2007.141440 PubMedCrossRefGoogle Scholar
  11. Edman KA (2010) Contractile performance of striated muscle. Adv Exp Med Biol 682:7–40. doi: 10.1007/978-1-4419-6366-6_2 PubMedCrossRefGoogle Scholar
  12. Edman KA, Tsuchiya T (1996) Strain of passive elements during force enhancement by stretch in frog muscle fibres. J Physiol 490(Pt 1):191–205PubMedGoogle Scholar
  13. Edman KA, Elzinga G, Noble MI (1978) Enhancement of mechanical performance by stretch during tetanic contractions of vertebrate skeletal muscle fibres. J Physiol 281:139–155PubMedGoogle Scholar
  14. Edman KA, Elzinga G, Noble MI (1982) Residual force enhancement after stretch of contracting frog single muscle fibers. J Gen Physiol 80(5):769–784PubMedCrossRefGoogle Scholar
  15. Givli S (2010) Towards multi-scale modeling of muscle fibers with sarcomere non-uniformities. J Theor Biol 264(3):882–892. doi: 10.1016/j.jtbi.2010.02.048 PubMedCrossRefGoogle Scholar
  16. Herzog W, Leonard TR (2000) The history dependence of force production in mammalian skeletal muscle following stretch-shortening and shortening-stretch cycles. J Biomech 33(5):531–542. doi: S0021-9290(99)00221-3 [pii] PubMedCrossRefGoogle Scholar
  17. Herzog W, Leonard TR (2002) Force enhancement following stretching of skeletal muscle: a new mechanism. J Exp Biol 205(Pt 9):1275–1283PubMedGoogle Scholar
  18. Herzog W, Leonard TR (2006) Response to the (Morgan and Proske) Letter to the Editor by Walter Herzog (on behalf of the authors) and Tim Leonard. J Physiol. doi: 10.1113/jphysiol.2006.125443
  19. Herzog W, Lee EJ, Rassier DE (2006) Residual force enhancement in skeletal muscle. J Physiol 574(Pt 3):635–642. doi: 10.1113/jphysiol.2006.107748 PubMedCrossRefGoogle Scholar
  20. Herzog W, Leonard TR, Joumaa V, Mehta A (2008) Mysteries of muscle contraction. J Appl Biomech 24(1):1–13PubMedGoogle Scholar
  21. Hisey B, Leonard TR, Herzog W (2009) Does residual force enhancement increase with increasing stretch magnitudes? J Biomech 42(10):1488–1492. doi: 10.1016/j.jbiomech.2009.03.046 PubMedCrossRefGoogle Scholar
  22. Huxley AF (1957) Muscle structure and theories of contraction. Prog Biophys Biophys Chem 7:255–318PubMedGoogle Scholar
  23. Iwaki M, Iwane AH, Shimokawa T, Cooke R, Yanagida T (2009) Brownian search-and-catch mechanism for myosin-VI steps. Nat Chem Biol 5(6):403–405. doi: 10.1038/nchembio.171 PubMedCrossRefGoogle Scholar
  24. Joumaa V, Rassier DE, Leonard TR, Herzog W (2007) Passive force enhancement in single myofibrils. Pflugers Arch 455(2):367–371. doi: 10.1007/s00424-007-0287-2 PubMedCrossRefGoogle Scholar
  25. Joumaa V, Leonard TR, Herzog W (2008a) Residual force enhancement in myofibrils and sarcomeres. Proc R Soc Lond B 275(1641):1411–1419. doi: 10.1098/rspb.2008.0142 CrossRefGoogle Scholar
  26. Joumaa V, Rassier DE, Leonard TR, Herzog W (2008b) The origin of passive force enhancement in skeletal muscle. Am J Physiol Cell Physiol 294(1):C74–78. doi: 10.1152/ajpcell.00218.2007 PubMedCrossRefGoogle Scholar
  27. Julian FJ, Morgan DL (1979a) The effect on tension of non-uniform distribution of length changes applied to frog muscle fibres. J Physiol 293:379–392PubMedGoogle Scholar
  28. Julian FJ, Morgan DL (1979b) Intersarcomere dynamics during fixed-end tetanic contractions of frog muscle fibres. J Physiol 293:365–378PubMedGoogle Scholar
  29. Kellermayer MS, Granzier HL (1996) Calcium-dependent inhibition of in vitro thin-filament motility by native titin. FEBS Lett 380(3):281–286. doi: 0014-5793(96)00055-5 [pii] PubMedCrossRefGoogle Scholar
  30. Labeit D, Watanabe K, Witt C, Fujita H, Wu Y, Lahmers S, Funck T, Labeit S, Granzier H (2003) Calcium-dependent molecular spring elements in the giant protein titin. Proc Natl Acad Sci USA 100(23):13716–13721. doi: 10.1073/pnas.2235652100 PubMedCrossRefGoogle Scholar
  31. Leonard TR, Herzog W (2010) Regulation of muscle force in the absence of actin-myosin-based cross-bridge interaction. Am J Physiol Cell Physiol 299(1):C14–20. doi: 10.1152/ajpcell.00049.2010 PubMedCrossRefGoogle Scholar
  32. Leonard T, Duvall M, Herzog W (2010) Force enhancement following stretch in a single sarcomere. Am J Physiol Cell Physiol 299(6):C1398–C1401. doi: 10.1152/ajpcell.00222.2010 PubMedCrossRefGoogle Scholar
  33. Mehta A, Herzog W (2008) Cross-bridge induced force enhancement? J Biomech 41(7):1611–1615. doi: 10.1016/j.jbiomech.2008.02.010 PubMedCrossRefGoogle Scholar
  34. Morgan DL (1990) New insights into the behavior of muscle during active lengthening. Biophys J 57(2):209–221. doi: 10.1016/S0006-3495(90)82524-8 PubMedCrossRefGoogle Scholar
  35. Morgan DL (1994) An explanation for residual increased tension in striated muscle after stretch during contraction. Exp Physiol 79(5):831–838PubMedGoogle Scholar
  36. Morgan DL, Proske U (2006) Sarcomere popping requires stretch over a range where total tension decreases with length. J Physiol 574(Pt 2):627–628; author reply 629–630. doi: 10.1113/jphysiol.2006.574201 Google Scholar
  37. Morgan DL, Proske U (2007) Can all residual force enhancement be explained by sarcomere non-uniformities? J Physiol 578(Pt 2):613–615; author reply 617–620. doi: 10.1113/jphysiol.2006.125039
  38. Morgan DL, Whitehead NP, Wise AK, Gregory JE, Proske U (2000) Tension changes in the cat soleus muscle following slow stretch or shortening of the contracting muscle. J Physiol 522(Pt 3):503–513PubMedCrossRefGoogle Scholar
  39. Peterson DR, Rassier DE, Herzog W (2004) Force enhancement in single skeletal muscle fibres on the ascending limb of the force-length relationship. J Exp Biol 207(Pt 16):2787–2791. doi: 10.1242/jeb.01095 PubMedCrossRefGoogle Scholar
  40. Pinniger GJ, Ranatunga KW, Offer GW (2006) Crossbridge and non-crossbridge contributions to tension in lengthening rat muscle: force-induced reversal of the power stroke. J Physiol 573(Pt 3):627–643. doi: 10.1113/jphysiol.2005.095448 PubMedCrossRefGoogle Scholar
  41. Pun C, Syed A, Rassier DE (2010) History-dependent properties of skeletal muscle myofibrils contracting along the ascending limb of the force-length relationship. Proc R Soc Lond B 277(1680):475–484. doi: 10.1098/rspb.2009.1579 CrossRefGoogle Scholar
  42. Rassier DE (2008) Pre-power stroke cross bridges contribute to force during stretch of skeletal muscle myofibrils. Proc R Soc Lond B 275(1651):2577–2586. doi: 10.1098/rspb.2008.0719 CrossRefGoogle Scholar
  43. Rassier DE, Herzog W (2004a) Active force inhibition and stretch-induced force enhancement in frog muscle treated with BDM. J Appl Physiol 97(4):1395–1400. doi: 10.1152/japplphysiol.00377.2004 PubMedCrossRefGoogle Scholar
  44. Rassier DE, Herzog W (2004b) Effects of shortening on stretch-induced force enhancement in single skeletal muscle fibers. J Biomech 37(9):1305–1312. doi: 10.1016/j.jbiomech.2003.12.033 PubMedCrossRefGoogle Scholar
  45. Rode C, Siebert T, Blickhan R (2009) Titin-induced force enhancement and force depression: a 'sticky-spring' mechanism in muscle contractions? J Theor Biol 259(2):350–360. doi: 10.1016/j.jtbi.2009.03.015 PubMedCrossRefGoogle Scholar
  46. Stoecker U, Telley IA, Stussi E, Denoth J (2009) A multisegmental cross-bridge kinetics model of the myofibril. J Theor Biol 259(4):714–726. doi: 10.1016/j.jtbi.2009.03.032 PubMedCrossRefGoogle Scholar
  47. Telley IA, Denoth J (2007) Sarcomere dynamics during muscular contraction and their implications to muscle function. J Muscle Res Cell Motil 28(1):89–104. doi: 10.1007/s10974-007-9107-8 PubMedCrossRefGoogle Scholar
  48. Telley IA, Denoth J, Ranatunga KW (2003) Inter-sarcomere dynamics in muscle fibres. A neglected subject? Adv Exp Med Biol 538:481–500, discussion 500PubMedCrossRefGoogle Scholar
  49. Telley IA, Denoth J, Stüssi E, Pfitzer G, Stehle R (2006a) Half-sarcomere dynamics in myofibrils during activation and relaxation studied by tracking fluorescent markers. Biophys J 90(2):514–530. doi: 10.1529/biophysj.105.070334 PubMedCrossRefGoogle Scholar
  50. Telley IA, Stehle R, Ranatunga KW, Pfitzer G, Stüssi E, Denoth J (2006b) Dynamic behaviour of half-sarcomeres during and after stretch in activated rabbit psoas myofibrils: sarcomere asymmetry but no 'sarcomere popping'. J Physiol 573(Pt 1):173–185. doi: 10.1113/jphysiol.2006.105809 PubMedCrossRefGoogle Scholar
  51. Veigel C, Molloy JE, Schmitz S, Kendrick-Jones J (2003) Load-dependent kinetics of force production by smooth muscle myosin measured with optical tweezers. Nat Cell Biol 5(11):980–986. doi: 10.1038/ncb1060 PubMedCrossRefGoogle Scholar
  52. Walcott S, Herzog W (2008) Modeling residual force enhancement with generic cross-bridge models. Math Biosci 216(2):172–186. doi: 10.1016/j.mbs.2008.10.005 PubMedCrossRefGoogle Scholar
  53. Walcott S, Sun SX (2009) Hysteresis in cross-bridge models of muscle. Phys Chem Chem Phys 11(24):4871–4881. doi: 10.1039/b900551j PubMedCrossRefGoogle Scholar
  54. Yamasaki R, Berri M, Wu Y, Trombitas K, McNabb M, Kellermayer MS, Witt C, Labeit D, Labeit S, Greaser M, Granzier H (2001) Titin-actin interaction in mouse myocardium: passive tension modulation and its regulation by calcium/S100A1. Biophys J 81(4):2297–2313. doi: 10.1016/S0006-3495(01)75876-6 PubMedCrossRefGoogle Scholar

Copyright information

© International Union for Pure and Applied Biophysics (IUPAB) and Springer 2011

Authors and Affiliations

  1. 1.Department of Physiology and Center for Muscle BiologyUniversity of KentuckyLexingtonUSA
  2. 2.Department of PhysiologyMS508 Chandler Medical CenterLexingtonUSA

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