Global and local tension measurements in biomimetic skeletal muscle tissues reveals early mechanical homeostasis

Abstract

Tension and mechanical properties of muscle tissue are tightly related to proper skeletal muscle function, which makes experimental access to the biomechanics of muscle tissue formation a key requirement to advance our understanding of muscle function and development. Recently developed elastic in vitro culture chambers allow for raising 3D muscle tissue under controlled conditions and to measure global tissue force generation. However, these chambers are inherently incompatible with high resolution microscopy limiting their usability to global force measurements, and preventing the exploitation of modern fluorescence based investigation methods for live and dynamic measurements. Here we present a new chamber design pairing global force measurements, quantified from post deflection, with local tension measurements obtained from elastic hydrogel beads embedded in muscle tissue. High resolution 3D video microscopy of engineered muscle formation, enabled by the new chamber, shows an early mechanical tissue homeostasis that remains stable in spite of continued myotube maturation.

The desmin mutation R349P increases contractility and fragility of stem cell‐generated muscle micro‐tissues

“…Typical values of muscle tension are 675 ± 123 Pa (mean ± SD, n = 8) during single twitch stimulation, and 871 ± 114 Pa during tetanic stimulation. Other studies reported slightly higher twitch tensions between 1 and 2 kPa for micro‐tissues grown from C2C12 skeletal muscle cells [20,21], and 1.7 kPa for micro‐tissues grown from satellite cells [35]. For comparison, intact soleus (SOL) and extensor digitorum longus (EDL) muscles of young/adult mice generate tetanic tensions of around 150–220 kPa (SOL) and 200–240 kPa (EDL), respectively [38–40].…”

“…The force generation of this tissue can be measured by the deflection of the flexible pillars. 3‐D micro‐tissues grown from skeletal muscle cell sources can thus be used as a platform for studying physiological and mechanical properties of muscles [20,21], for drug testing [22,23], and for disease modelling [23–25].…”

Visualizing the Invisible: Advanced Optical Microscopy as a Tool to Measure Biomechanical Forces

“…The premise of target-based methods is to measure the shape change of an introduced object with a known stiffness. This has been achieved with liquid microdroplets or micron-scale polyacrylamide spheres, enabling investigators to study phenomena such as tissue morphogenesis ( Campàs et al, 2014 ; Serwane et al, 2017 ; Mongera et al, 2018 ; Träber et al, 2019 ; Hofemeier et al, 2021 ), interstitial pressure in tumor growth ( Dolega et al, 2017 ; Lee et al, 2019 ), and phagocytosis ( Vorselen et al, 2020 , 2021 ). However, none of the methods discussed so far directly identify the molecular source from which a force is potentiated.…”

Aorta smooth muscle-on-a-chip reveals impaired mitochondrial dynamics as a therapeutic target for aortic aneurysm in bicuspid aortic valve disease

“…Therefore, these models may not provide sufficient information of pathogenesis and drug response of BAV-TAA. Owing to the bioengineering advance, microfluidic-based organ-on-chip models have been widely developed to replicates human tissue microenvironment for toxicity analysis, drug screening and disease modeling and thus promotes pharmaceutical translation from preclinical studies to clinical trials ( Zhang et al, 2018 ; Ingber, 2016 ; Park et al, 2019 ; Thacker et al, 2020 ; Hofemeier et al, 2021 ). It provides an opportunity to use a novel platform to study BAV-TAA on a susceptible human genetic background and may fill the gap between animal and human medicine.…”