Regulation of cardiomyocyte adhesion and mechanosignalling through distinct nanoscale behaviour of integrin ligands mimicking healthy or fibrotic extracellular matrix.
Regulation of cardiomyocyte adhesion and mechanosignalling through distinct nanoscale behaviour of integrin ligands mimicking healthy or fibrotic extracellular matrix.
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DOI：
10.1098/rstb.2022.0021
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发表时间：
2022-11-21
影响因子：
6.3
通讯作者：
Iskratsch, Thomas
中科院分区：
文献类型：
--
作者：
Hawkes, William;Marhuenda, Emilie;Reynolds, Paul;O'Neill, Caoimhe;Pandey, Pragati;Wilson, Darren Graham Samuel;Freeley, Mark;Huang, Da;Hu, Junquiang;Gondarenko, Sasha;Hone, James;Gadegaard, Nikolaj;Palma, Matteo;Iskratsch, Thomas
关键词：
心血管环境的硬度在衰老和疾病中发生变化，并有助于疾病的发病率和进展。改变胶原表达和交联调节心脏细胞外基质（ECM）的刚性。此外，基底层糖蛋白，特别是层粘连蛋白和纤维连接蛋白调节心肌细胞粘连形成、力学和机械信号。层粘连蛋白在健康心脏中含量丰富，但纤维连接蛋白在纤维化心脏中表达增多。ECM受体与改变的ECM共同调节。由于整合素动力学、聚类和下游粘附形成的差异，预计最终会影响心肌细胞的机械信号传导；然而，细节仍然难以捉摸。在这里，我们试图研究不同的心肌细胞整合素/配体组合如何影响粘附形成，牵引力和机械信号传导，使用具有定义刚度的均匀涂层表面，聚二甲基硅氧烷纳米柱，微图和专门设计的精确配体呈现的生物纳米阵列的组合。因此，我们发现新生大鼠心肌细胞（表达层粘连蛋白和纤维连接蛋白结合的整合素）的粘附纳米级组织、信号传导和牵引力的产生强烈依赖于整合素/配体的组合。综上所述，我们的数据表明，纤维连接蛋白的存在与纤维化区域硬度的增强相结合，将强烈影响心肌细胞的行为并影响疾病的进展。这篇文章是主题问题“心肌细胞：在生长、健康和疾病中结构和功能之间相互作用的新启示”的一部分。
The stiffness of the cardiovascular environment changes during ageing and in disease and contributes to disease incidence and progression. Changing collagen expression and cross-linking regulate the rigidity of the cardiac extracellular matrix (ECM). Additionally, basal lamina glycoproteins, especially laminin and fibronectin regulate cardiomyocyte adhesion formation, mechanics and mechanosignalling. Laminin is abundant in the healthy heart, but fibronectin is increasingly expressed in the fibrotic heart. ECM receptors are co-regulated with the changing ECM. Owing to differences in integrin dynamics, clustering and downstream adhesion formation this is expected to ultimately influence cardiomyocyte mechanosignalling; however, details remain elusive. Here, we sought to investigate how different cardiomyocyte integrin/ligand combinations affect adhesion formation, traction forces and mechanosignalling, using a combination of uniformly coated surfaces with defined stiffness, polydimethylsiloxane nanopillars, micropatterning and specifically designed bionanoarrays for precise ligand presentation. Thereby we found that the adhesion nanoscale organization, signalling and traction force generation of neonatal rat cardiomyocytes (which express both laminin and fibronectin binding integrins) are strongly dependent on the integrin/ligand combination. Together our data indicate that the presence of fibronectin in combination with the enhanced stiffness in fibrotic areas will strongly impact on the cardiomyocyte behaviour and influence disease progression. This article is part of the theme issue ‘The cardiomyocyte: new revelations on the interplay between architecture and function in growth, health, and disease’.
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影响因子：
20.1
作者：
Ljubojevic-Holzer S;Herren AW;Djalinac N;Voglhuber J;Morotti S;Holzer M;Wood BM;Abdellatif M;Matzer I;Sacherer M;Radulovic S;Wallner M;Ivanov M;Wagner S;Sossalla S;von Lewinski D;Pieske B;Brown JH;Sedej S;Bossuyt J;Bers DM
通讯作者：
Bers DM
影响因子：
20.1
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Anderson ME
影响因子：
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Glancy, Brian;Balaban, Robert S.
通讯作者：
Balaban, Robert S.
影响因子：
20.1
作者：
Liu T;Yang N;Sidor A;O'Rourke B
通讯作者：
O'Rourke B
影响因子：
5.4
作者：
García-Rivas, GD;Guerrero-Hernández, A;Zazueta, C
通讯作者：
Zazueta, C