ABSTRACT
Quantification of skeletal muscle functional strength is essential to assess the outcomes of therapeutic procedures for muscular disorders. Several muscle three-dimensional “Organ-on-chip” models have been developed to measure the generated force. Yet, these technologies require a substantial amount of biological material, which is problematic in the context of limited patient sample.
Here we developed a miniaturized 3D myotube culture chip with contraction monitoring capacity. Combination of light-induced molecular adsorption technology and optimized micropatterned substrate design enabled to obtain high culture yields in tightly controlled physical and chemical microenvironments. Spontaneous twitch contractions in 3D myotubes derived from primary human myoblasts were observed, the generated force was measured and the contraction pattern characterized. In addition, the impact of three-dimensional culture on nuclear morphology was analyzed, confirming the similarity in organization between the obtained 3D myotubes and in vivo myofibers. Our system enabled to model LMNA-related Congenital Muscular Dystrophy (L-CMD) with successful development of mutant 3D myotubes displaying contractile dysfunction.
We anticipate that this technology shall be used to study contraction characteristics and evaluate how specific diseases affect muscle organization and force generation. Our downsized model system might allow to substantially improve drug screening capability for therapeutic oriented research.
Competing Interest Statement
The authors have declared no competing interest.
