Canović Elizabeth P, Zollinger Alicia J, Tam Sze Nok, Smith Michael L, Stamenović Dimitrije
Department of Biomedical Engineering, Boston University, Boston, Massachusetts; and.
Department of Biomedical Engineering, Boston University, Boston, Massachusetts; and Division of Material Science and Engineering, Boston University, Brookline, Massachusetts
Am J Physiol Cell Physiol. 2016 Sep 1;311(3):C528-35. doi: 10.1152/ajpcell.00037.2016. Epub 2016 Aug 3.
Mammalian cells of various types exhibit the remarkable ability to adapt to externally applied mechanical stresses and strains. Because of this adaptation, cells can maintain their endogenous mechanical tension at a preferred (homeostatic) level, which is essential for normal physiological functions of cells and tissues and provides protection against various diseases, including atherosclerosis and cancer. Conventional wisdom is that the cell possesses the ability to maintain tensional homeostasis on its own. Recent findings showed, however, that isolated cells cannot maintain tensional homeostasis. Here we studied the effect of multicellular interactions on tensional homeostasis by measuring traction forces in isolated bovine aortic endothelial cells and in confluent and nonconfluent cell clusters of different sizes. We found that, in isolated cells, the traction field exhibited a highly dynamic and erratic behavior. However, in cell clusters, dynamic fluctuations of the traction field became attenuated with increasing cluster size, at a rate that was faster in nonconfluent than confluent clusters. The driving mechanism of attenuation of traction field fluctuations was statistical averaging of the noise, and the impeding mechanism was nonuniform stress distribution in the clusters, which resulted from intercellular force transmission, known as a "global tug-of-war." These results show that isolated cells could not maintain tensional homeostasis, which confirms previous findings, and that tensional homeostasis is a multicellular phenomenon, which is a novel finding.
各种类型的哺乳动物细胞都表现出显著的能力，能够适应外部施加的机械应力和应变。由于这种适应性，细胞能够将其内源性机械张力维持在一个优选的（稳态的）水平，这对于细胞和组织的正常生理功能至关重要，并能提供针对包括动脉粥样硬化和癌症在内的各种疾病的保护。传统观点认为细胞自身具备维持张力稳态的能力。然而，最近的研究结果表明，分离的细胞无法维持张力稳态。在这里，我们通过测量分离的牛主动脉内皮细胞以及不同大小的汇合和未汇合细胞簇中的牵引力，研究了多细胞相互作用对张力稳态的影响。我们发现，在分离的细胞中，牵引场表现出高度动态和不稳定的行为。然而，在细胞簇中，牵引场的动态波动随着簇大小的增加而减弱，在未汇合簇中的减弱速度比汇合簇更快。牵引场波动减弱的驱动机制是噪声的统计平均，而阻碍机制是簇中应力分布不均匀，这是由细胞间力传递导致的，即所谓的“全局拔河”。这些结果表明，分离的细胞无法维持张力稳态，这证实了先前的研究结果，并且张力稳态是一种多细胞现象，这是一个新的发现。
