工程微心肌描述心肌组织收缩性的细胞和细胞外调节。

IF 1.4 4区 生物学 Q4 CELL BIOLOGY
Nethika R Ariyasinghe, Caitlin H Reck, Alyssa A Viscio, Andrew P Petersen, Davi M Lyra-Leite, Nathan Cho, Megan L McCain
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引用次数: 0

摘要

心血管疾病是导致死亡的主要原因,部分原因是由于现有心肌模型的局限性。心肌由排列整齐、可收缩的心肌细胞组成,其间散布着合成细胞外基质(ECM)的成纤维细胞。许多不同心脏疾病中ECM重构的细胞统计学、生化和力学特性。然而,各种细胞和细胞外重构对心肌收缩输出的影响尚不清楚。为了解决这个问题,我们用纤维连接蛋白(FN)或层粘连蛋白(LN)对齐的正方形对13 kPa和90 kPa聚丙烯酰胺凝胶进行了微图案化。我们用两种浓度的原代新生大鼠心室肌细胞播种凝胶,其中天然含有成纤维细胞。细胞聚集成排列的“μ心肌”与成纤维细胞:肌细胞比例依赖于初始播种浓度。利用牵引力显微镜(TFM),我们发现不同条件下的峰值收缩纵向横截面力相似,但90 kPa凝胶的峰值收缩功明显较低。这表明,在调节收缩输出方面,ECM弹性优于ECM配体和细胞人口统计学。因为我们的平台提供了对细胞-细胞和细胞-基质相互作用的独立控制,它在心脏病建模方面有许多应用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Engineering micromyocardium to delineate cellular and extracellular regulation of myocardial tissue contractility.

Cardiovascular diseases are a leading cause of death, in part due to limitations of existing models of the myocardium. Myocardium consists of aligned, contractile cardiac myocytes interspersed with fibroblasts that synthesize extracellular matrix (ECM). The cellular demographics and biochemical and mechanical properties of the ECM remodel in many different cardiac diseases. However, the impact of diverse cellular and extracellular remodeling on the contractile output of the myocardium are poorly understood. To address this, we micropatterned 13 kPa and 90 kPa polyacrylamide gels with aligned squares of fibronectin (FN) or laminin (LN). We seeded gels with two concentrations of primary neonatal rat ventricular myocytes, which naturally contain fibroblasts. Cells assembled into aligned "μMyocardia" with fibroblast : myocyte ratios dependent on initial seeding concentration. Using traction force microscopy (TFM), we found that the peak systolic longitudinal cross-sectional force was similar across conditions, but the peak systolic work was significantly lower on 90 kPa gels. This indicates that ECM elasticity dominates over ECM ligand and cell demographics in regulating contractile output. Because our platform provides independent control over cell-cell and cell-matrix interactions, it has many applications for cardiac disease modeling.

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来源期刊
Integrative Biology
Integrative Biology 生物-细胞生物学
CiteScore
4.90
自引率
0.00%
发文量
15
审稿时长
1 months
期刊介绍: Integrative Biology publishes original biological research based on innovative experimental and theoretical methodologies that answer biological questions. The journal is multi- and inter-disciplinary, calling upon expertise and technologies from the physical sciences, engineering, computation, imaging, and mathematics to address critical questions in biological systems. Research using experimental or computational quantitative technologies to characterise biological systems at the molecular, cellular, tissue and population levels is welcomed. Of particular interest are submissions contributing to quantitative understanding of how component properties at one level in the dimensional scale (nano to micro) determine system behaviour at a higher level of complexity. Studies of synthetic systems, whether used to elucidate fundamental principles of biological function or as the basis for novel applications are also of interest.
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