Cavendish Laboratory, Department of Physics, University of Cambridge, Cambridge, United Kingdom.
PLoS One. 2012;7(9):e45237. doi: 10.1371/journal.pone.0045237. Epub 2012 Sep 27.
Although cellular mechanical properties are known to alter during stem cell differentiation, understanding of the functional relevance of such alterations is incomplete. Here, we show that during the course of differentiation of human myeloid precursor cells into three different lineages, the cells alter their viscoelastic properties, measured using an optical stretcher, to suit their ultimate fate and function. Myeloid cells circulating in blood have to be advected through constrictions in blood vessels, engendering the need for compliance at short time-scales (<seconds). Intriguingly, only the two circulating myeloid cell types have increased short time scale compliance and flow better through microfluidic constrictions. Moreover, all three differentiated cell types reduce their steady-state viscosity by more than 50% and show over 140% relative increase in their ability to migrate through tissue-like pores at long time-scales (>minutes), compared to undifferentiated cells. These findings suggest that reduction in steady-state viscosity is a physiological adaptation for enhanced migration through tissues. Our results indicate that the material properties of cells define their function, can be used as a cell differentiation marker and could serve as target for novel therapies.
虽然已知细胞的力学性质在干细胞分化过程中会发生改变，但对于这种改变的功能相关性的理解还不完全。在这里，我们表明，在人类髓系前体细胞分化为三种不同谱系的过程中，细胞改变了它们的粘弹性特性，使用光学拉伸仪进行测量，以适应它们最终的命运和功能。在血液中循环的髓系细胞必须通过血管中的狭窄部位进行被动输送，这就需要在短时间尺度（<秒）内具有顺应性。有趣的是，只有两种循环的髓系细胞类型具有增加的短时间尺度顺应性，并且能够更好地通过微流控狭窄部位流动。此外，与未分化细胞相比，所有三种分化的细胞类型的稳态粘度降低超过 50%，并且在长时间尺度（>分钟）通过类似组织的孔迁移的能力增加了 140%以上。这些发现表明，稳态粘度的降低是增强通过组织迁移的生理适应。我们的结果表明，细胞的物质特性决定了它们的功能，可以用作细胞分化的标志物，并可作为新型治疗方法的靶点。
