Mechanical principles of effects of botulinum toxin on muscle length-force characteristics: an assessment by finite element modeling.
Recent experiments involving muscle force measurements over a range of muscle lengths show that effects of botulinum toxin (BTX) are complex e.g., force reduction varies as a function of muscle length. We hypothesized that altered conditions of sarcomeres within active parts of partially paralyzed muscle is responsible for this effect. Using finite element modeling, the aim was to test this hypothesis and to study principles of how partial activation as a consequence of BTX affects muscle mechanics. In order to model the paralyzing effect of BTX, only 50% of the fascicles (most proximal, or middle, or most distal) of the modeled muscle were activated. For all muscle lengths, a vast majority of sarcomeres of these BTX-cases were at higher lengths than identical sarcomeres of the BTX-free muscle. Due to such "longer sarcomere effect", activated muscle parts show an enhanced potential of active force exertion (up to 14.5%). Therefore, a muscle force reduction originating exclusively from the paralyzed muscle fiber populations, is compromised by the changes of active sarcomeres leading to a smaller net force reduction. Moreover, such "compromise to force reduction" varies as a function of muscle length and is a key determinant of muscle length dependence of force reduction caused by BTX. Due to longer sarcomere effect, muscle optimum length tends to shift to a lower muscle length. Muscle fiber-extracellular matrix interactions occurring via their mutual connections along full peripheral fiber lengths (i.e., myofascial force transmission) are central to these effects. Our results may help improving our understanding of mechanisms of how the toxin secondarily affects the muscle mechanically.
Biomedical Engineering Institute, Boğaziçi University, Istanbul 34684, Turkey.
Ahu N
AN
Turkoglu
Research Instituut 'Move Amsterdam', Faculteit Bewegingswetenschappen, Vrije Universiteit, Amsterdam, The Netherlands.
Peter A
PA
Huijing
Biomedical Engineering Institute, Boğaziçi University, Istanbul 34684, Turkey. Electronic address: can.yucesoy@boun.edu.tr.
Can A
CA
Yucesoy
D000818:Animals; D001696:Biomechanical Phenomena; D001905:Botulinum Toxins / Q000494:pharmacology*; D005109:Extracellular Matrix; D020342:Finite Element Analysis; D008954:Models, Biological; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D012518:Sarcomeres / Q000187:drug effects / Q000502:physiology
D001905:Botulinum Toxins
Botulinum toxin; Finite element analysis; Muscle length dependent force reduction; Muscle length–force characteristics; Myofascial force transmission; Sarcomere length