Lalli Mark L, Asthagiri Anand R
Department of Chemical Engineering, Northeastern University, Boston, MA.
Department of Chemical Engineering, Northeastern University, Boston, MA ; Department of Bioengineering, Northeastern University, Boston, MA.
Cell Mol Bioeng. 2015 Jun 1;8(2):247-257. doi: 10.1007/s12195-015-0383-x. Epub 2015 Mar 8.
During development and disease, cells migrate collectively in response to gradients in physical, chemical and electrical cues. Despite its physiological significance and potential therapeutic applications, electrotactic collective cell movement is relatively less well understood. Here, we analyze the combined effect of intercellular interactions and electric fields on the directional migration of non-transformed mammary epithelial cells, MCF-10A. Our data show that clustered cells exhibit greater sensitivity to applied electric fields but align more slowly than isolated cells. Clustered cells achieve half-maximal directedness with an electric field that is 50% weaker than that required by isolated cells; however, clustered cells take ∼2-4 fold longer to align. This trade-off in greater sensitivity and slower dynamics correlates with the slower speed and intrinsic directedness of collective movement even in the absence of an electric field. Whereas isolated cells exhibit a persistent random walk, the trajectories of clustered cells are more ballistic as evidenced by the superlinear dependence of their mean square displacement on time. Thus, intrinsically-directed, slower clustered cells take longer to redirect and align with an electric field. These findings help to define the operating space and the engineering trade-offs for using electric fields to affect cell movement in biomedical applications.
在发育和疾病过程中,细胞会根据物理、化学和电信号梯度进行集体迁移。尽管电趋性集体细胞运动具有生理意义和潜在的治疗应用,但人们对其了解相对较少。在这里,我们分析了细胞间相互作用和电场对未转化的乳腺上皮细胞MCF-10A定向迁移的综合影响。我们的数据表明,聚集的细胞对施加的电场表现出更高的敏感性,但比孤立的细胞排列得更慢。聚集的细胞在电场强度比孤立细胞所需电场强度弱50%时达到最大定向性的一半;然而,聚集的细胞排列所需时间要长2至4倍。这种更高敏感性和更慢动力学之间的权衡与即使在没有电场的情况下集体运动的较慢速度和内在定向性相关。孤立的细胞表现出持续的随机游走,而聚集细胞的轨迹更具弹道性,其均方位移对时间的超线性依赖证明了这一点。因此,内在定向、速度较慢的聚集细胞需要更长时间来重新定向并与电场对齐。这些发现有助于定义在生物医学应用中利用电场影响细胞运动的操作空间和工程权衡。