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Characterization of the Viscoelastic Properties of Ovarian Cancer Cells Membranes by Optical Tweezers and Quantitative Phase Imaging
Frontiers in Physics ( IF 3.1 ) Pub Date : 2020-10-05 , DOI: 10.3389/fphy.2020.582956
Thompson Lu , Bahman Anvari

Ovarian cancer is the deadliest gynecological cancer in women. It is a highly metastatic disease with pelvis, regional lymph nodes, and peritoneal cavity as major sites for tumor deposits. Mechanical properties of ovarian cancer cells can play a major role in metastasis as the cells detach from the ovaries and undergo deformation during the metastatic process. Herein, we have characterized the viscoelastic properties of the plasma membrane of normal epithelial (IOSE364) and cancerous (SKOV3) ovarian cells by optical tweezers and quantitative phase imaging. Using optical tweezers, we obtained time-resolved force profiles associated with membrane tethers pulled from the cells. We used quantitative phase imaging to measure the diameter of membrane tethers, and subsequently, estimated the membrane bending modulus and membrane tension in the tether. Our results indicate that the force (190 ± 76 pN) (mean ± standard deviation) required to separate the membrane of SKOV3 cells from the cytoskeleton was significantly lower (p = 0.0004) than the force (350 ± 81 pN) for IOSE364 cells. The mean stiffness (2.8 ± 0.8 pN/μm) of membrane tethers pulled from SKOV3 cells was significantly lower (p = 0.032) than the value for IOSE 364 cells (3.7 ± 0.8 pN/μm). Mean value of the force relaxation characteristic time associated with diffusive flow of lipids was also significantly lower (p = 0.018) for SKOV3 membranes (12.9 ± 6.9 s) as compared to the value for IOSE 364 membranes (20.4 ± 6.2 s). Similarly, the mean value of the membrane bending modulus for SKOV3 cells [(0.51 ± 0.23) × 10–18 J] was significantly lower (p = 0.007) than the value for IOSE364 cells [(1.29 ± 0.32) × 10–18 J]. Overall, our results suggest that the membranes of SKOV3 cells are less resistant to mechanical deformation. Increased membrane susceptibility to mechanical deformation may be a facilitating factor in the metastatic behavior of cancerous ovarian cells. Characterization of membrane biomechanics may provide a useful diagnostic biomarker for assessment of the metastatic potential of ovarian cancer, and a target for development of therapeutics.



中文翻译:

光学镊子和定量相成像表征卵巢癌细胞膜的粘弹性。

卵巢癌是女性中最致命的妇科癌症。它是一种高度转移性疾病,骨盆,局部淋巴结和腹膜腔为肿瘤沉积的主要部位。卵巢癌细胞的机械特性在转移过程中起着重要作用,因为这些细胞会从卵巢脱离并在转移过程中发生变形。在这里,我们已经表征了正常镊子(IOSE364)和癌细胞(SKOV3)卵巢细胞质膜的粘弹性特性,通过光镊和定量相成像。使用光镊,我们获得了与时间间隔有关的力分布,这些力分布与从细胞中拉出的膜系绳有关。我们使用定量相位成像技术来测量膜系链的直径,然后估算系链中的膜弯曲模量和膜张力。p= 0.0004),而不是IOSE364电池的力(350±81 pN)。从SKOV3细胞拉出的膜系链的平均刚度(2.8±0.8 pN /μm)明显较低(p= 0.032),而不是IOSE 364细胞的值(3.7±0.8 pN /μm)。与脂质的扩散流相关的力松弛特征时间的平均值也显着较低(pSKOV3膜(12.9±6.9 s)= 0.018),而IOSE 364膜(20.4±6.2 s)= 0.018)。同样,SKOV3细胞的膜弯曲模量平均值[(0.51±0.23)×10 –18  J]明显较低(p= 0.007)比IOSE364单元的值[(1.29±0.32)×10 –18  J]。总的来说,我们的结果表明SKOV3细胞的膜对机械变形的抵抗力较小。膜对机械变形的敏感性增加可能是卵巢癌细胞转移行为的促进因素。膜生物力学的表征可以为评估卵巢癌的转移潜力提供有用的诊断生物标志物,并为治疗方法的开发提供目标。

更新日期:2020-11-12
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