Titin mechanism on skeletal muscles: Active force

İskelet kaslarında titin mekanizması: Aktif kuvvet

Atilla Şahan, Alay Kesler, Kaan Salman, Hilal Kılınç, Aykut Hocalar, Yeliz Kahraman

*Correspondence: PhD. Yeliz KAHRAMAN yelizkahramana@hotmail.com.

 ¹Burdur Mehmet Akif University and Sport Science, Antalya, Turkey, atilla_sahan3543@hotmail.com Orcid: 0009-0000-7185-2348

²Associate., İstanbul Cerrahpaşa University and Sport Science Faculty, İstanbul, Turkey, alayk@hotmail.com Orcid: 0000-0002-7232-6072

³Research associate., Muğla Sıtkı Koçman University and Sport Science Faculty, Muğla, Turkey, kaansalman@mu.edu.tr Orcid: 0000-0002-2425-2128

⁴Associate profesör., Dokuz Eylül University, Sport Science Faculty, İzmir, Turkey, kilinc.hilal@deu.edu.tr Orcid: 0000-0001-6348-9753

⁵Ph.d., Akdeniz University, Health Science Institute, Antalya, Turkey, aykuthocalar@gmail.com Orcid: 0009-0009-5708-4683

⁶PhD. Akdeniz University and Health Science Institute, Antalya, Turkey, yelizkahramana@hotmail.com orcid: 0000-0001-8209-4087

Doi: https://doi.org/10.5281/zenodo.20993999

https://www.ijoss.org/Archive/v3-i2/ijoss-Volume3-issue2-07.pdf

Download Full Text

Received / Gönderim: 02.05.2026 Accepted / Kabul: 12.06.2026 Published / Yayın: 23.06.2026

Abstract

Titin molecules of skeletal muscle actived muscle gene expression produce active force during passive stiffness indirectly in spring properties. To that the titin activation determines on passive sarcomeres role and active force during molecular lengthening in myofibrils. Titin directly of thick (myosin) and thin (actin) filament localization to enable processes of myofibril elasticities promote molecular energy in sarcomeres. These characteristic physiologic results determine muscle force reactivation both as passive and active muscle. The induction of titin binding to Ca2+ reactivation low and high energy accumulation as (%15), titin directly activated to mechanic force with increasing of Ca2+ as (%85). This suggest noted that sarcomere’s PEVK region segmental myofibril composition provides isometric force through elongation arranged on entropy low energy whereas enthalpy high energy. In these direction produce force of connectin (titin) owing to a spring role to slow-twitch fiber than fast-twitch fiber during isometric contraction. After activated force recruit passive elements enable to isometric force. Outcomes of titin, molecular spring properties accompany with active force with passive elements, thus this reported that titin structural condition during force producing changes on active force along with passive stiffness.

Keywords: Titin molecule, spring role, active force, passive tension. 

Özet

İskelet kasının aktif genindeki titin molekülleri, pasif sertlik sırasında dolaylı olarak yay özelliklerine bağlı aktif kuvvet üretir. Bu nedenle titin aktivasyonu, pasif sarkomerlerin rolünü ve miyofibrillerdeki moleküler uzama sırasında aktif kuvveti belirler. Titin, miyofibril elastikiyet süreçlerini mümkün kılmak için kalın (miyozin) ve ince (aktin) filamentlerin lokalizasyonunu doğrudan etkileyerek sarkomerlerde moleküler enerjiyi artırır. Bu karakteristik fizyolojik sonuçlar, kas kuvvetinin hem pasif hem de aktif kas olarak yeniden aktivasyonunu belirler. Titin bağlanmasının Ca2+ ile indüklenmesi düşük ve yüksek enerji birikimini (%15) yeniden aktive ederken, titin Ca2+ artışıyla (%85) mekanik kuvvete doğrudan aktif olur. Kısacası, sarkomerin PEVK bölgesindeki segmental miyofibril bileşimi, düşük enerjili entropi ve yüksek enerjili entalpiye göre düzenlenmiş uzama yoluyla izometrik kuvvet sağlar. Bu yönde, izo-koşulda hızlı kas liflerinden ziyade yavaş kas liflerinde yay rolü oluşumunda konnektin (titin) kuvveti üretilir. Aktif hale gelen kuvvet, pasif elemanları harekete geçirerek izometrik kuvveti mümkün kılar. Titin molekülünün yay özelliklerinin sonuçları, aktif kuvvet ve pasif unsurlarla birlikte ortaya çıkar; bu nedenle, aktif kuvvet ve pasif sertlik ile birlikte kuvvet üretimi sırasında titin yapısal olarak değişmektedir.

Anahtar Kelimeler: Titin molekülü, yay rolü, aktif kuvvet, pasif gerilim.

How to Cite This Article

APA 7:

 Şahan, A., Kesler, A., Salman, K., Kılınç, H., Hocalar, A., & Kahraman, Y. (2026). Titin mechanism on skeletal muscles: Active force. International Journal of Health, Exercise, and Sport Sciences (IJOSS), 3(2), 509–517. https://www.ijoss.org/Archive/v3-i2/ijoss-Volume3-issue2-07.pdf

Vancouver: 
Şahan A, Kesler A, Salman K, Kılınç H, Hocalar A, Kahraman Y. Titin mechanism on skeletal muscles: Active force. Int J Health Exerc Sport Sci (IJOSS). 2026;3(2):509-517. Available from: https://www.ijoss.org/Archive/v3-i2/ijoss-Volume3-issue2-07.pdf

References / Kaynaklar

• Adewale, A. O., & Ahn, Y. H. (2021). Titin N2A Domain and Its Interactions at the Sarcomere. International journal of molecular sciences, 22(14), 7563. https://doi.org/10.3390/ijms22147563.
• Bang, M. L., Centner, T., Fornoff, F., Geach, A. J., Gotthardt, M., McNabb, M., Witt, C. C., Labeit, D., Gregorio, C. C., Granzier, H., & Labeit, S. (2001). The complete gene sequence of titin, expression of an unusual approximately 700-kDa titin isoform, and its interaction with obscurin identify a novel Z-line to I-band linking system. Circulation research, 89(11), 1065–1072. https://doi.org/10.1161/hh2301.100981.
• Bennett, P. M., Hodkin, T. E., & Hawkins, C. (1997). Evidence that the tandem Ig domains near the end of the muscle thick filament form an inelastic part of the I-band titin. Journal of structural biology, 120(1), 93–104. https://doi.org/10.1006/jsbi.1997.3898.
• Cooper, G.M. (2000) The Cell: A Molecular Approach. 2nd Edition, Sunderland (MA): Sinauer Associates, The Development and Causes of Cancer.
• Forbes, J. G., Jin, A. J., Ma, K., Gutierrez-Cruz, G., Tsai, W. L., & Wang, K. (2005). Titin PEVK segment: charge-driven elasticity of the open and flexible polyampholyte. Journal of muscle research and cell motility, 26(6-8), 291–301. https://doi.org/10.1007/s10974-005-9035-4.
• Freundt, J. K., & Linke, W. A. (2019). Titin as a force-generating muscle protein under regulatory control. Journal of applied physiology (Bethesda, Md. : 1985), 126(5), 1474–1482. https://doi.org/10.1152/japplphysiol.00865.2018.
• Gage, M., & Nishikawa, K. (2026). Roles of N2A Titin in Signaling and Muscle Mechanics. Medical Research Archives, 14(3). doi:10.18103/mra.v14i3.7328.
• Goto, K., Okuyama, R., Honda, M., Uchida, H., Akema, T., Ohira, Y., & Yoshioka, T. (2003). Profiles of connectin (titin) in atrophied soleus muscle induced by unloading of rats. Journal of applied physiology (Bethesda, Md. : 1985), 94(3), 897–902. https://doi.org/10.1152/japplphysiol.00408.2002.
• Hanson, J., & Huxley, H. E. (1953). Structural basis of the cross-striations in muscle. Nature, 172(4377), 530–532. https://doi.org/10.1038/172530b0.
• Horowits, R., & Podolsky, R. J. (1987). The positional stability of thick filaments in activated skeletal muscle depends on sarcomere length: evidence for the role of titin filaments. The Journal of cell biology, 105(5), 2217–2223. https://doi.org/10.1083/jcb.105.5.2217.
• Horowits R. (1992). Passive force generation and titin isoforms in mammalian skeletal muscle. Biophysical journal, 61(2), 392–398. https://doi.org/10.1016/S0006-3495(92)81845-3.
• Hoyle G. (1983). Forms of modulatable tension in skeletal muscles. Comparative biochemistry and physiology. A, Comparative physiology, 76(2), 203–210. https://doi.org/10.1016/0300-9629(83)90316-x.
• Huxley H. E. (1953). Electron microscope studies of the organisation of the filaments in striated muscle. Biochimica et biophysica acta, 12(3), 387–394. https://doi.org/10.1016/0006-3002(53)90156-5.
• Joumaa, V., Bertrand, F., Liu, S., Poscente, S., & Herzog, W. (2018). Does partial titin degradation affect sarcomere length nonuniformities and force in active and passive myofibrils?. American journal of physiology. Cell physiology, 315(3), C310–C318. https://doi.org/10.1152/ajpcell.00183.2017.
• Kloock, L., Lauren de Graaf, M.,  Boström, K.J., Wagner, H. (2026). Spring–damper titin model improves the estimation of muscle forces during force enhancement measurements, Journal of Biomechanics, 2, 113306. https://doi.org/10.1016/j.jbiomech.2026.113306.
• Leonard, T. R., & Herzog, W. (2010). Regulation of muscle force in the absence of actin-myosin-based cross-bridge interaction. American journal of physiology. Cell physiology, 299(1), C14–C20. https://doi.org/10.1152/ajpcell.00049.2010.
• Loreau, V., Koolhaas, W. H., Chan, E. H., De Boissier, P., Brouilly, N., Avosani, S., Sane, A., Pitaval, C., Reiter, S., Luis, N. M., Mangeol, P., von Philipsborn, A. C., Rupprecht, J. F., Görlich, D., Habermann, B. H., & Schnorrer, F. (2025). Titin-dependent biomechanical feedback tailors sarcomeres to specialized muscle functions in insects. Science advances, 11(19), eads8716. https://doi.org/10.1126/sciadv.ads8716.
• Maruyama K. (1976). Connectin, an elastic protein from myofibrils. Journal of biochemistry, 80(2), 405–407. https://doi.org/10.1093/oxfordjournals.jbchem.a131291.
• Monroy, J. A., Powers, K. L., Gilmore, L. A., Uyeno, T. A., Lindstedt, S. L., & Nishikawa, K. C. (2012). What is the role of titin in active muscle?. Exercise and sport sciences reviews, 40(2), 73–78. https://doi.org/10.1097/JES.0b013e3182458.
• Nishikawa, K. C., Monroy, J. A., Uyeno, T. E., Yeo, S. H., Pai, D. K., & Lindstedt, S. L. (2012). Is titin a ‘winding filament’? A new twist on muscle contraction. Proceedings. Biological sciences, 279(1730), 981–990. https://doi.org/10.1098/rspb.2011.1304.
• Nishikawa K. (2020). Titin: A Tunable Spring in Active Muscle. Physiology (Bethesda, Md.), 35(3), 209–217. https://doi.org/10.1152/physiol.00036.2019.
• Powers, K., Schappacher-Tilp, G., Jinha, A., Leonard, T., Nishikawa, K., & Herzog, W. (2014). Titin force is enhanced in actively stretched skeletal muscle. The Journal of experimental biology, 217(Pt 20), 3629–3636. https://doi.org/10.1242/jeb.105361.
• Stronczek, C., Lange, S., Bullard, B., Wolniak, S., Börgeson, E., Mayans, O., & Fleming, J. R. (2021). The N2A region of titin has a unique structural configuration. The Journal of general physiology, 153(7), e202012766. https://doi.org/10.1085/jgp.202012766.
• Young, P., & Gautel, M. (2000). The interaction of titin and alpha-actinin is controlled by a phospholipid-regulated intramolecular pseudoligand mechanism. The EMBO journal, 19(23), 6331–6340. https://doi.org/10.1093/emboj/19.23.6331.