![]() ![]() A more thorough mechanistic understanding of body-weight-sensitive molecular-level changes to the musculoskeletal system will greatly improve our understanding of the basic biology of musculoskeletal design and function during growth and across animal size ranges, and of disease (and aging) phenotypes that impair locomotion. I will address mainly animal systems here, but would like to point out that strong parallels exist between mechanobiology in animals and plants (for recent plant biomechanics reviews, see Moulia, 2013 Niklas et al., 2006). It is unclear whether there are any precise and absolute signals of body weight that are detected by some central body sensor(s) the mechanisms I discuss here can detect and/or produce signals that are proportional to body weight changes transmitted across musculoskeletal designs. In doing so, I will discuss gene regulatory mechanisms regulating muscle sarcomere molecular variation (such as alternative splicing) and highlight potential mechanosensitive mechanisms that can affect muscle properties at the molecular level. In this Commentary, I aim to present evidence for the less commonly discussed idea that the musculoskeletal system is also sensitive to body weight variation at the molecular level. This generality of design requirements and performance outcomes suggests that there are (phylogenetically) conserved mechanisms that have tuned (and continue to tune) both the gross morphology and the associated molecular level design of animal musculoskeletal systems to body weight variation in a quantitatively precise fashion. Indeed, Marden and Allen demonstrated that the maximum force output of most running, flying and swimming animal motors is proportional to motor mass ( Marden, 2005 Marden and Allen, 2002) and, therefore, to body mass, for many animals. This is particularly true for terrestrial and flying animals, but may even apply to aquatic animals (that experience variable degrees of buoyancy), which must move volumes of water equivalent to their body mass ( Bejan and Marden, 2006) in order to swim. The effect of gravity, the one truly constant environmental variable, on body mass (giving body weight, or body mass× g) must be resisted and overcome to achieve movement. The design of most animal locomotor systems appears to be constrained mainly by body weight and associated considerations of durability. Thus, I present a non-exhaustive overview of the evidence – drawn from different fields of study and different levels of biological organization – for the existence of body weight sensing mechanism(s). The main objective of this Commentary is to briefly summarize the former area of study but, in particular, to highlight the latter hypothesis and the relevance of understanding the mechanisms that control musculoskeletal function at the molecular level. that the molecular-level composition of musculoskeletal designs is sensitive to body weight variation – has been the subject of only minimal investigation. Although studies at the level of whole organisms and tissue morphology and function clearly indicate that musculoskeletal designs are constrained by body weight variation, the corollary to this – i.e. ![]() This implies the existence of evolutionarily conserved feedback between sensors that produce quantitative signals encoding body weight and proximate determinants of musculoskeletal designs. Animal species varying in size and musculoskeletal design all support and move their body weight. ![]()
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