Measurement of adherent cell mass and growth

Measurement of adherent cell mass and growth
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DOI:
10.1073/pnas.1011365107
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发表时间:
2010-11-30
影响因子:
11.1
通讯作者:
Bashir, Rashid
Bashir, Rashid
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Park, Kidong;Millet, Larry J.;Bashir, Rashid

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细胞的物理性质的表征,如它们的质量和刚度一直是极大的兴趣,并可以在细胞生物学,组织工程,癌症和疾病的研究具有深远的影响。例如,单个贴壁人细胞的细胞生长速率对细胞质量的直接依赖性可以阐明细胞周期进展的潜在机制。在这里,我们开发了一个阵列的微机电系统(MEMS)谐振质量传感器,可用于直接测量的生物物理特性,质量和生长速度的单个贴壁细胞。与传统的悬臂梁质量传感器不同,我们的传感器在细胞附着表面上保持均匀的质量灵敏度。通过测量具有生长(软)细胞和固定(硬)细胞的质量传感器的频移,并通过分析建模,我们推导出未固定细胞的杨氏模量,并解开细胞质量测量对细胞刚度的依赖性。最后,我们在质量传感器上培养单个细胞,并测量它们的质量超过50小时。我们的研究结果表明,贴壁的人结肠上皮细胞具有更大的细胞质量的生长速率增加,并且平均生长速率与细胞质量呈线性增加,为3.25%/hr。我们的灵敏质量传感器具有位置无关的质量灵敏度,可以与显微镜相结合,用于同时监测细胞生长和状态,并提供研究细胞生长,细胞周期进程,分化和凋亡。
The characterization of physical properties of cells such as their mass and stiffness has been of great interest and can have profound implications in cell biology, tissue engineering, cancer, and disease research. For example, the direct dependence of cell growth rate on cell mass for individual adherent human cells can elucidate the mechanisms underlying cell cycle progression. Here we develop an array of micro-electro-mechanical systems (MEMS) resonant mass sensors that can be used to directly measure the biophysical properties, mass, and growth rate of single adherent cells. Unlike conventional cantilever mass sensors, our sensors retain a uniform mass sensitivity over the cell attachment surface. By measuring the frequency shift of the mass sensors with growing (soft) cells and fixed (stiff) cells, and through analytical modeling, we derive the Young's modulus of the unfixed cell and unravel the dependence of the cell mass measurement on cell stiffness. Finally, we grew individual cells on the mass sensors and measured their mass for 50+ hours. Our results demonstrate that adherent human colon epithelial cells have increased growth rates with a larger cell mass, and the average growth rate increases linearly with the cell mass, at 3.25%/hr. Our sensitive mass sensors with a position-independent mass sensitivity can be coupled with microscopy for simultaneous monitoring of cell growth and status, and provide an ideal method to study cell growth, cell cycle progression, differentiation, and apoptosis.