Matrix architecture and mechanics regulate myofibril organization, costamere assembly, and contractility of engineered myocardial microtissues.
Matrix architecture and mechanics regulate myofibril organization, costamere assembly, and contractility of engineered myocardial microtissues.
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基质结构和力学调节肌原纤维组织、肋骨组装和工程心肌微组织的收缩性。
DOI：
10.1101/2023.10.20.563346
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Baker,BrendonM
中科院分区：
文献类型：
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作者：
DePalma,SamuelJ;Jillberto,Javiera;Stis,AustinE;Huang,DarcyD;Lo,Jason;Davidson,ChristopherD;Chowdhury,Aamilah;Jewett,MaggieE;Kobeissi,Hiba;Chen,ChristopherS;Lejeune,Emma;Helms,AdamS;Nordsletten,DavidA;Baker,BrendonM
心肌的机械功能由心肌细胞收缩性和细胞外基质（ECM）的生物力学定义。了解这种关系仍然是一个重要的未满足的挑战，由于在现有的方法工程心肌组织的限制。在这里，他们通过整合ECM模拟合成，纤维基质和诱导多能干细胞衍生的心肌细胞（iPSC-CM），建立了具有可调力学和结构的心脏微组织阵列，实现了真实的收缩力读数，深入的结构评估和组织特异性计算建模。他们发现基质纤维的刚度和排列明显影响纯iPSC-CM组织的结构发育和收缩功能。通过计算模型和定量免疫荧光对纤维基质硬度影响的进一步研究表明，肌原纤维组装、肌原纤维成熟和特别是肋节组装中的细胞-ECM相互作用与组织的收缩功能改善相关。这些结果强调了具有可控结构和力学的iPSC-CM组织模型如何能够阐明组织成熟和疾病的机制。
The mechanical function of the myocardium is defined by cardiomyocyte contractility and the biomechanics of the extracellular matrix (ECM). Understanding this relationship remains an important unmet challenge due to limitations in existing approaches for engineering myocardial tissue. Here, they established arrays of cardiac microtissues with tunable mechanics and architecture by integrating ECM‐mimetic synthetic, fiber matrices, and induced pluripotent stem cell‐derived cardiomyocytes (iPSC‐CMs), enabling real‐time contractility readouts, in‐depth structural assessment, and tissue‐specific computational modeling. They found that the stiffness and alignment of matrix fibers distinctly affect the structural development and contractile function of pure iPSC‐CM tissues. Further examination into the impact of fibrous matrix stiffness enabled by computational models and quantitative immunofluorescence implicates cell‐ECM interactions in myofibril assembly, myofibril maturation, and notably costamere assembly, which correlates with improved contractile function of tissues. These results highlight how iPSC‐CM tissue models with controllable architecture and mechanics can elucidate mechanisms of tissue maturation and disease.