Characterization of Single-Cell Osmotic Swelling Dynamics for New Physical Biomarkers
Characterization of Single-Cell Osmotic Swelling Dynamics for New Physical Biomarkers
复制标题
DOI：
10.1021/acs.analchem.0c02289
复制
发表时间：
2021-01-26
影响因子：
7.4
通讯作者：
Ding, Xiaoyun
中科院分区：
文献类型：
--
作者：
Fajrial, Apresio K.;Liu, Kun;Ding, Xiaoyun
细胞物理生物标志物的表征对于理解细胞特性至关重要，并且适用于疾病诊断。目前用于分析物理表型的方法涉及使细胞变形的外力。或者，通过渗透溶胀的内部张力也可以使细胞变形。然而，一个既定的假设认为，在低渗肿胀集中在质膜上产生的力是无法评估的物理性质的有核细胞。在这里，我们利用渗透膨胀的方法来表征不同类型的有核细胞。使用用于具有截断悬挂微柱的细胞捕获阵列的微流体装置（CellHangars），我们分离单细胞并以1秒的时间分辨率评估低渗挑战期间的溶胀动力学。我们证明了具有不同机械表型的细胞显示出独特的溶胀动力学特征。不同类型的细胞可以以高达99%的准确率进行分类。我们还表明，溶胀动力学可以检测由于细胞骨架破坏的细胞力学性质的变化。考虑到其简单性，溶胀动力学为细胞提供了一种宝贵的无标记物理生物标志物，在生物学研究和临床实践中具有潜在的应用。
Characterization of cell physical biomarkers is vital to understand cell properties and applicable for disease diagnostics. Current methods used to analyze physical phenotypes involve external forces to deform the cells. Alternatively, internal tension forces via osmotic swelling can also deform the cells. However, an established assumption contends that the forces generated during hypotonic swelling concentrated on the plasma membrane are incapable of assessing the physical properties of nucleated cells. Here, we utilized an osmotic swelling approach to characterize different types of nucleated cells. Using a microfluidic device for cell trapping arrays with truncated hanging micropillars (CellHangars), we isolated single cells and evaluated the swelling dynamics during the hypotonic challenge at 1 s time resolution. We demonstrated that cells with different mechanical phenotypes showed unique swelling dynamics signature. Different types of cells can be classified with an accuracy of up to similar to 99%. We also showed that swelling dynamics can detect cellular mechanical property changes due to cytoskeleton disruption. Considering its simplicity, swelling dynamics offers an invaluable label-free physical biomarker for cells with potential applications in both biological studies and clinical practice.