Center for Intelligent Biomaterials, Department of Chemistry, University of Massachusetts, Lowell, MA 01854, USA.
Anal Biochem. 2012 Feb 1;421(1):164-71. doi: 10.1016/j.ab.2011.10.052. Epub 2011 Nov 7.
During transformation of a normal cell to a cell capable of forming a cancerous growth, cellular morphology, the cytoskeleton, and focal contacts undergo significant changes. These changes should be capable of being characterized via real-time monitoring of the dynamic cell adhesion process and viscoelastic properties of cells. Here, we describe use of the quartz crystal microbalance (QCM) to distinguish the dynamic cell adhesion signatures of human normal (HMEC) versus malignant (MCF-7) mammary epithelial cells. The significantly reduced QCM responses (changes in frequency [Δf] and motional resistance ΔR) of MCF-7 cells compared with those of HMECs mirror the cancer cells' morphological features as observed via optical microscope. We analyzed the initial 2-h cell adhesion kinetics, suggesting cell-cell cooperativity for HMECs and no or weak cell-cell interactions for MCF-7 cells. We propose that changes of the ΔR/Δf ratio, which we term the cell viscoelastic index (CVI), reflect the establishment of cytoskeleton structure and dynamic viscoelastic properties of living cells. The CVI decreases significantly on initiation of cell to surface interactions as cells establish their cytoskeletal structures. During the cell adhesion process, MCF-7 cells were consistently softer, exhibiting up to a 2.5-fold smaller CVI when compared with HMECs.
在正常细胞向能够形成癌性生长的细胞转化的过程中,细胞形态、细胞骨架和焦点接触会发生重大变化。这些变化应该能够通过实时监测动态细胞黏附过程和细胞的黏弹性特性来表征。在这里,我们描述了使用石英晶体微天平(QCM)来区分人正常(HMEC)和恶性(MCF-7)乳腺上皮细胞的动态细胞黏附特征。与 HMEC 相比,MCF-7 细胞的 QCM 响应(频率[Δf]和动态电阻ΔR 的变化)显著降低,反映了癌细胞的形态特征,这些特征可以通过光学显微镜观察到。我们分析了最初 2 小时的细胞黏附动力学,表明 HMEC 细胞具有细胞间协同作用,而 MCF-7 细胞则没有或只有较弱的细胞间相互作用。我们提出,ΔR/Δf 比值的变化,我们称之为细胞黏弹性指数(CVI),反映了细胞骨架结构和活细胞动态黏弹性的建立。当细胞建立其细胞骨架结构时,细胞与表面相互作用的初始阶段 CVI 显著降低。在细胞黏附过程中,MCF-7 细胞始终更柔软,其 CVI 比 HMEC 小 2.5 倍。