Department of Electrical and Computer Engineering, Micro and Nanotechnology Laboratory, and Beckman Institute of Advanced Science and Technology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
Proc Natl Acad Sci U S A. 2010 Nov 30;107(48):20691-6. doi: 10.1073/pnas.1011365107. Epub 2010 Nov 10.
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.
细胞物理特性的描述，如质量和刚性，一直受到广泛关注，并可能对细胞生物学、组织工程、癌症和疾病研究产生深远影响。例如，单个贴壁人细胞的细胞生长速率与细胞质量的直接依赖性可以阐明细胞周期进程的机制。在这里，我们开发了一系列微机电系统（MEMS）谐振质量传感器，可用于直接测量单个贴壁细胞的生物物理特性、质量和生长速率。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保持均匀的质量灵敏度。通过测量生长（软）细胞和固定（硬）细胞的质量传感器的频率偏移，并通过分析建模，我们得出了未固定细胞的杨氏模量，并揭示了细胞质量测量对细胞刚性的依赖性。最后，我们将单个细胞种植在质量传感器上，并测量它们 50 多个小时的质量。我们的结果表明，贴壁的人结肠上皮细胞的生长速率随着细胞质量的增加而增加，平均生长速率与细胞质量呈线性关系，为 3.25%/hr。我们的具有位置无关质量灵敏度的灵敏质量传感器可以与显微镜结合使用，用于同时监测细胞生长和状态，并提供了一种研究细胞生长、细胞周期进程、分化和凋亡的理想方法。
