Ko Eunkyung, Aydin Onur, Li Zhengwei, Gapinske Lauren, Huang Kai-Yu, Saif Taher, Bashir Rashid, Kong Hyunjoon
Department of Bioengineering, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA; Micro and Nanotechnology Laboratory, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA; Carl R. Woese Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, IL, USA.
Department of Mechanical Science and Engineering, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
Biomaterials. 2022 Aug;287:121643. doi: 10.1016/j.biomaterials.2022.121643. Epub 2022 Jun 24.
Engineered skeletal muscle act as therapeutics invaluable to treat injured or diseased muscle and a "living" material essential to assemble biological machinery. For normal development, skeletal myoblasts should express connexin 43, one of the gap junction proteins that promote myoblast fusion and myogenesis, during the early differentiation stage. However, myoblasts cultured in vitro often down-regulate connexin 43 before differentiation, limiting myogenesis and muscle contraction. This study demonstrates that tethering myoblasts with reduced graphene oxide (rGO) slows connexin 43 regression during early differentiation and increases myogenic mRNA synthesis. The whole RNA sequencing also confirms that the rGO on cells increases regulator genes for myogenesis, including troponin, while decreasing negative regulator genes. The resulting myotubes generated a three-fold larger contraction force than the rGO-free myotubes. Accordingly, a valveless biohybrid pump assembled with the rGO-tethered muscle increased the fluid velocity and flow rate considerably. The results of this study would provide an important foundation for developing physiologically relevant muscle and powering up biomachines that will be used for various bioscience studies and unexplored applications.
工程化骨骼肌作为治疗受伤或患病肌肉的宝贵疗法，以及组装生物机器必不可少的“活体”材料。对于正常发育，骨骼肌成肌细胞在早期分化阶段应表达连接蛋白43，它是促进成肌细胞融合和肌生成的间隙连接蛋白之一。然而，体外培养的成肌细胞在分化前常常下调连接蛋白43，限制了肌生成和肌肉收缩。本研究表明，用还原氧化石墨烯（rGO）束缚成肌细胞可减缓早期分化过程中连接蛋白43的消退，并增加肌生成mRNA的合成。全RNA测序还证实，细胞上的rGO增加了包括肌钙蛋白在内的肌生成调节基因，同时减少了负调节基因。由此产生的肌管产生的收缩力比无rGO的肌管大三倍。因此，用rGO束缚的肌肉组装的无阀生物杂交泵显著提高了流体速度和流速。本研究结果将为开发生理相关肌肉以及为用于各种生物科学研究和未探索应用的生物机器提供动力奠定重要基础。
