The contribution of cellular mechanotransduction to cardiomyocyte form and function.
The contribution of cellular mechanotransduction to cardiomyocyte form and function.
复制标题
细胞力转导对心肌细胞形式和功能的贡献。
DOI：
10.1007/s10237-012-0419-2
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发表时间：
2012-11
影响因子：
3.5
通讯作者：
Parker, Kevin Kit
中科院分区：
文献类型：
--
作者：
Sheehy, Sean P.;Grosberg, Anna;Parker, Kevin Kit
心肌发育受到一系列精心编排的信号事件的调控，这些信号事件由多种形式的中间体介导。细胞分化和成熟是一系列纵向整合过程的一部分，这些过程跨越多个空间和时间尺度，形成一个明确的细胞集合体，能够在器官水平上协同且可靠地发挥作用。早期理解心肌细胞命运决定的分子机制的研究主要集中在这一过程的遗传和化学介质上。然而，越来越多的证据表明，细胞外基质（ECM）与细胞表面受体之间的机械相互作用以及相邻细胞之间的物理相互作用在调节控制心脏发育过程的信号通路中起着重要作用。跨学科研究表明，ECM对细胞行为的影响通过多种物理机制发生，例如ECM边界条件、弹性以及机械信号向细胞核等细胞内区室的传递。除了实验研究外，还开发了许多数学模型，试图捕捉细胞与其局部微环境之间的相互作用以及这些相互作用对细胞自组装和功能行为的影响。然而，关于心肌细胞与其环境之间的物理相互作用如何转化为生化细胞反应的机制，以及如何在体外利用这些信号模式从干细胞衍生的心肌细胞制造更能忠实代表其体内对应物的心肌组织构建体，仍有许多问题未得到解答。这些研究代表了一种广泛的努力，即将生物形态描述为一种信息传递的渠道，其范围从蛋白质的纳米尺度到患者的米尺度，并可能对机械转导在心脏发育和疾病中的作用产生新的见解。
Myocardial development is regulated by an elegantly choreographed ensemble of signaling events mediated by a multitude of intermediates that take a variety of forms. Cellular differentiation and maturation are a subset of vertically integrated processes that extend over several spatial and temporal scales to create a well-defined collective of cells that are able to function cooperatively and reliably at the organ level. Early efforts to understand the molecular mechanisms of cardiomyocyte fate determination focused primarily on genetic and chemical mediators of this process. However, increasing evidence suggests that mechanical interactions between the extracellular matrix (ECM) and cell surface receptors as well as physical interactions between neighboring cells play important roles in regulating the signaling pathways controlling the developmental processes of the heart. Interdisciplinary efforts have made it apparent that the influence of the ECM on cellular behavior occurs through a multitude of physical mechanisms, such as ECM boundary conditions, elasticity, and the propagation of mechanical signals to intracellular compartments, such as the nucleus. In addition to experimental studies, a number of mathematical models have been developed that attempt to capture the interplay between cells and their local microenvironment and the influence these interactions have on cellular self-assembly and functional behavior. Nevertheless, many questions remain unanswered concerning the mechanism through which physical interactions between cardiomyocytes and their environment are translated into biochemical cellular responses and how these signaling modalities can be utilized in vitro to fabricate myocardial tissue constructs from stem cell-derived cardiomyocytes that more faithfully represent their in vivo counterpart. These studies represent a broad effort to characterize biological form as a conduit for information transfer that spans the nanometer length scale of proteins to the meter length scale of the patient and may yield new insights into the contribution of mechanotransduction into heart development and disease.
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DOI：
10.1111/j.1540-8167.2007.00959.x
发表时间：
2007-12-01
影响因子：
2.7
作者：
Chung, Chiung-Yin;Bien, Harold;Entcheva, Emilia
通讯作者：
Entcheva, Emilia
影响因子：
7.8
作者：
Belkin, AM;Zhidkova, NI;Balzac, F;Altruda, F;Tomatis, D;Maier, A;Tarone, G;Koteliansky, VE;Burridge, K
通讯作者：
Burridge, K
影响因子：
--
作者：
Bray, Mark-Anthony;Sheehy, Sean P.;Parker, Kevin Kit
通讯作者：
Parker, Kevin Kit
影响因子：
4.8
作者：
Brancaccio, M;Guazzone, S;Silengo, L
通讯作者：
Silengo, L
DOI：
10.1039/c1ib00061f
发表时间：
2011-11
期刊：
Integrative biology : quantitative biosciences from nano to macro
影响因子：
--
作者：
Alford PW;Nesmith AP;Seywerd JN;Grosberg A;Parker KK
通讯作者：
Parker KK