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基于原子力显微镜(AFM)的细胞黏弹特性测量与分析
Alternative TitleMeasurement and analysis of cellular viscoelastic properties using atomic force microscopy
党丹1; 李密2,3; 项荣武1
Department机器人学研究室
Source Publication科学通报
ISSN0023-074X
2019
Volume64Issue:15Pages:1610-1619
Indexed ByEI ; CSCD
EI Accession number20192607106221
CSCD IDCSCD:6511619
Contribution Rank2
Funding Organization国家自然科学基金(61873258, 61503372) ; 中国科学院青年创新促进会项目(2017243)
Keyword原子力显微镜 细胞机械特性 压痕技术 黏弹特性 松弛时间
Abstract细胞机械特性在细胞生理病理变化过程中起着重要指示作用,对其进行研究有助于了解生命活动奥秘以及疾病发生发展的内在机理.原子力显微镜(AFM)的发明为单细胞机械特性研究提供了新的技术手段,给细胞力学及癌症等重大疾病带来了大量新的认识.然而现有AFM细胞机械特性探测主要集中在细胞弹性特性,对细胞黏弹特性进行的研究和分析还较为缺乏.本文基于AFM开展了细胞黏弹特性测量和分析研究.首先建立了基于AFM单细胞压痕技术的细胞黏弹特性探测方法,基于此实现了对6种不同类型细胞(包括贴壁细胞、悬浮细胞、正常细胞、癌细胞、细胞系和原代细胞等)黏弹特性(松弛时间)的测量与表征,随后对测量结果进行回归分析揭示出细胞1阶松弛时间和2阶松弛时间之间的关联.研究结果加深了人们对细胞黏弹特性的认识,为单细胞机械特性研究提供了新的思路.
Other AbstractCell mechanics plays an important role in cellular physiological and pathological processes. During the formation and progression of tumors, the alterations in the mechanics of cancerous cells and tumor micro-environment promote the growth and migration of cancerous cells. Hence, investigating cell mechanics is of crucial significance in understanding the underlying mechanisms regulating life activities and diseases. The advent of atomic force microscopy (AFM) provides a powerful tool for detecting the mechanical properties of single cells. Compared with other single-cell mechanical analysis techniques, the advantage of AFM is that AFM is able to simultaneously obtain the topography and mechanics of cells, which is particularly useful for investigating the correlation between cell structures and cell mechanics. The biomedical applications of AFM in single-cell mechanics provide considerable novel insights into how cell and tissue mechanics affect tumor development and metastasis, contributing much to the communities of biomechanics and biophysics. However, current AFM single-cell mechanical experiments are commonly performed on measuring the elastic properties of cells and studies about the viscoelastic properties of cells are still scarce. In this work, AFM was utilized to measure and analyze the viscoelastic properties of cells. First, the detailed procedure of detecting the viscoelasticity of cells based on AFM indentation technique was established. AFM probe was controlled to perform approach-dwell-retract movement on cells in the vertical direction. During the approach-dwell-retract process, the deflection of AFM cantilever versus time was recorded, which yielded the force-time (F-T) curves. The original F-T curves were then normalized and fitted by two-order Maxwell model, which gave two cellular relaxation times (the first relaxation time τ1 and the second relaxation time τ2). The fitting results showed that the theoretical curve matched the experimental relaxation curve well, indicating that the two-order Maxwell model was suited for characterizing the relaxation behaviors of cells. Second, the established procedure was used to measure the relaxation time of six different types of cells, including mammalian adherent cells, mammalian suspended cells, normal cells, cancerous cells, cell lines cultured in vitro and primary cells prepared from bone marrow and peripheral blood of healthy volunteers. The fitting curves were consistent with the experimental relaxation curves for all of the six types of cells used here, indicating the effectiveness of the presented method for detecting the viscoelastic properties of cells. Besides, the results showed the various cellular relaxation times for the different types of cells. The statistical results showed that the first cellular relaxation times were in the range 0.01−0.03 s, which might correspond to the behaviors of cytoplasm. The second cellular relaxation time was in the range 0.2−0.4 s, which might correspond to the behaviors of the cytoskeleton. Finally, regression analysis was performed on the measured cellular relaxation times, showing the linear relationship between the first cellular relaxation time τ1 and the second cellular relaxation time τ2, and the regression coefficients were variable for different types of cells. The research improves our understanding of cellular viscoelasticity and also provides a novel idea to measure the viscoelastic properties of cells, which will have potential impacts on cell mechanics and biomedicine.
Language中文
Citation statistics
Document Type期刊论文
Identifierhttp://ir.sia.cn/handle/173321/24576
Collection机器人学研究室
Corresponding Author党丹; 李密
Affiliation1.沈阳药科大学医疗器械学院
2.中国科学院沈阳自动化研究所机器人学国家重点实验室
3.中国科学院机器人与智能制造创新研究院
Recommended Citation
GB/T 7714
党丹,李密,项荣武. 基于原子力显微镜(AFM)的细胞黏弹特性测量与分析[J]. 科学通报,2019,64(15):1610-1619.
APA 党丹,李密,&项荣武.(2019).基于原子力显微镜(AFM)的细胞黏弹特性测量与分析.科学通报,64(15),1610-1619.
MLA 党丹,et al."基于原子力显微镜(AFM)的细胞黏弹特性测量与分析".科学通报 64.15(2019):1610-1619.
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