The effects of a skeletal muscle titin mutation on walking in mice

Pace, Cinnamon M.; Mortimer, Sarah; Monroy, Jenna A.; Nishikawa, Kiisa C.

doi:10.1007/s00359-016-1137-5

Cited by 6 publications

(10 citation statements)

References 35 publications

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“…In contrast to expectations based on age-related degeneration of mdm muscles, correlation analysis (Table 1) showed that neither muscle mass nor passive stress at L 0 +10% was significantly related to age in wild-type or mdm muscles (all P>0.05). Our previous studies showed that mdm mice and their muscles are small, not because they degenerate over time, but rather because growth stops at an early age (Pace et al, 2017). In contrast to expectations based on age-related muscle degeneration, we also found that maximum isometric stress increased significantly with age (Table 1) in our sample of mdm muscles (n=7, P=0.0055) but not in wild-type muscles (n=8, P=0.2859).…”

Section: Resultscontrasting

confidence: 79%

Effects of a titin mutation on force enhancement and force depression in mouse soleus muscles

Tahir

Monroy

Rice

et al. 2020

Journal of Experimental Biology

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The active isometric force produced by muscles varies with muscle length in accordance with the force-length relationship. Compared with isometric contractions at the same final length, force increases after active lengthening (force enhancement) and decreases after active shortening (force depression). In addition to cross-bridges, titin has been suggested to contribute to force enhancement and depression. Although titin is too compliant in passive muscles to contribute to active tension at short sarcomere lengths on the ascending limb and plateau of the force-length relationship, recent evidence suggests that activation increases titin stiffness. To test the hypothesis that titin plays a role in force enhancement and depression, we investigated isovelocity stretching and shortening in active and passive wild-type and mdm (muscular dystrophy with myositis) soleus muscles. Skeletal muscles from mdm mice have a small deletion in the N2A region of titin and show no increase in titin stiffness during active stretch. We found that: (1) force enhancement and depression were reduced in mdm soleus compared with wildtype muscles relative to passive force after stretch or shortening to the same final length; (2) force enhancement and force depression increased with amplitude of stretch across all activation levels in wildtype muscles; and (3) maximum shortening velocity of wild-type and mdm muscles estimated from isovelocity experiments was similar, although active stress was reduced in mdm compared with wild-type muscles. The results of this study suggest a role for titin in force enhancement and depression, which contribute importantly to muscle force during natural movements.

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Section: Resultscontrasting

confidence: 79%

Effects of a titin mutation on force enhancement and force depression in mouse soleus muscles

Tahir

Monroy

Rice

et al. 2020

Journal of Experimental Biology

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“…Compared with WT mice, mdm mice exhibit a nearly complete absence of ankle dorsiflexion at the start of the stance phase (Pace et al, 2017), despite the fact that the ankle range of motion is normal during manipulation of the joint. During walking, energy absorbed by the posterior muscles of the shank is subsequently recovered to amplify work and power during plantarflexion (Lipfert et al, 2014;Roberts and Azizi, 2011).…”

Section: Comparison Between In Vitro and In Vivo Muscle Workmentioning

confidence: 93%

“…It is interesting to consider how the deficit in negative work in mdm muscles might affect locomotor biomechanics in the mouse. Pace et al (2017) compared limb morphology and walking kinematics between mdm and WT mice. They found that differences in limb proportions (i.e.…”

Section: Comparison Between In Vitro and In Vivo Muscle Workmentioning

confidence: 99%

“…Therefore, reduced dorsiflexion likely limits the speed and efficiency of walking in mdm mice. Pace et al (2017) concluded that an increase in passive stiffness of mdm muscles (Monroy et al, 2017) and other compensatory mechanisms may lead to reduced ankle range of motion to protect the shank muscles from damage. Our results support this interpretation.…”

Section: Comparison Between In Vitro and In Vivo Muscle Workmentioning

confidence: 99%

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Effects of a titin mutation on negative work during stretch-shortening cycles in skeletal muscles

Hessel

Nishikawa

2017

Journal of Experimental Biology

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Negative work occurs in muscles during braking movements such as downhill walking or landing after a jump. When performing negative work during stretch-shortening cycles, viscoelastic structures within muscles store energy during stretch, return a fraction of this energy during shortening and dissipate the remaining energy as heat. Because tendons and extracellular matrix are relatively elastic rather than viscoelastic, energy is mainly dissipated by cross bridges and titin. Recent studies demonstrate that titin stiffness increases in active skeletal muscles, suggesting that titin contributions to negative work may have been underestimated in previous studies. The muscular dystrophy with myositis () mutation in mice results in a deletion in titin that leads to reduced titin stiffness in active muscle, providing an opportunity to investigate the contribution of titin to negative work in stretch-shortening cycles. Using the work loop technique, extensor digitorum longus and soleus muscles from and wild-type (WT) mice were stimulated during the stretch phase of stretch-shortening cycles to investigate negative work. The results demonstrate that, compared with WT muscles, negative work is reduced in muscles from mice. We suggest that changes in the viscoelastic properties of titin reduce energy storage by muscles during stretch and energy dissipation during shortening. Maximum isometric stress is also reduced in muscles from mice, possibly due to impaired transmission of cross-bridge force, impaired cross-bridge function or both. Functionally, the reduction in negative work could lead to increased muscle damage during eccentric contractions that occur during braking movements.

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“…However, controlled eccentric activity immediately prior to shortening, termed a stretch‐shortening cycle (SSC) or countermovement, increases shortening force (Abbott and Aubert, ; Cavagna et al, ; Cavagna and Citterio, ; Gregor et al, ; Finni et al, 2000). An abundance of evidence suggests that elastic energy storage in tendons and titin—a large, calcium‐dependent, spring‐like protein spanning half of the sarcomere—underlies the enhanced and increased metabolic efficiency of force production during SSCs and may actually protect the sarcomeres from damage during whole muscle stretch (Edman et al, ; Roberts et al, ; Biewener et al, ; Joumaa et al, ; Leonard et al, ,b; Nishikawa et al, ; Joumaa and Herzog, ; Azizi and Roberts, ; Holt et al, ; Konow et al, ; Monroy et al, ; Powers et al, ; Pace et al, ). Indeed, Herzog and colleagues () argue that titin should be considered a third myofilament alongside actin and myosin due to its substantial contributions to force production during active fiber lengthening.…”

Section: Parameters Of Performancementioning

confidence: 99%

Dynamic Musculoskeletal Functional Morphology: Integrating diceCT and XROMM

Orsbon

Gidmark

Ross

2018

The Anatomical Record

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The tradeoff between force and velocity in skeletal muscle is a fundamental constraint on vertebrate musculoskeletal design (form:function relationships). Understanding how and why different lineages address this biomechanical problem is an important goal of vertebrate musculoskeletal functional morphology. Our ability to answer questions about the different solutions to this tradeoff has been significantly improved by recent advances in techniques for quantifying musculoskeletal morphology and movement. Herein, we have three objectives: (1) review the morphological and physiological parameters that affect muscle function and how these parameters interact; (2) discuss the necessity of integrating morphological and physiological lines of evidence to understand muscle function and the new, high resolution imaging technologies that do so; and (3) present a method that integrates high spatiotemporal resolution motion capture (XROMM, including its corollary fluoromicrometry), high resolution soft tissue imaging (diceCT), and electromyography to study musculoskeletal dynamics in vivo. The method is demonstrated using a case study of in vivo primate hyolingual biomechanics during chewing and swallowing. A sensitivity analysis demonstrates that small deviations in reconstructed hyoid muscle attachment site location introduce an average error of 13.2% to in vivo muscle kinematics. The observed hyoid and muscle kinematics suggest that hyoid elevation is produced by multiple muscles and that fascicle rotation and tendon strain decouple fascicle strain from hyoid movement and whole muscle length. Lastly, we highlight current limitations of these techniques, some of which will likely soon be overcome through methodological improvements, and some of which are inherent. Anat Rec, 301:378-406, 2018. © 2018 Wiley Periodicals, Inc.

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The effects of a skeletal muscle titin mutation on walking in mice

Cited by 6 publications

References 35 publications

Effects of a titin mutation on force enhancement and force depression in mouse soleus muscles

Effects of a titin mutation on force enhancement and force depression in mouse soleus muscles

Effects of a titin mutation on negative work during stretch-shortening cycles in skeletal muscles

Dynamic Musculoskeletal Functional Morphology: Integrating diceCT and XROMM

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