UC Berkeley

The mechanical properties of cells provide valuable information regarding biological and clinically relevant cellular characteristics. In this dissertation, we demonstrate two new microfluidic platforms, mechano-node-pore sensing (mechano-NPS) and visco-node-pore sensing (visco-NPS), to characterize cellular mechanical behavior. Mechano-NPS is a multi- parametric single-cell-analysis method to quantify simultaneously cell diameter, resistance to compressive deformation, transverse deformation under constant strain, and recovery time after deformation. We define a new parameter, the whole-cell deformability index (wCDI), which provides a quantitative mechanical metric of the resistance to compressive deformation that can be used to discriminate among different cell types. The wCDI and the transverse deformation under constant strain show malignant MCF-7 and A549 cell lines are mechanically distinct from non-malignant, MCF-10A and BEAS-2B cell lines. We categorize cell recovery time and show that the composition of recovery types, which is a consequence of changes in cytoskeletal organization, correlates with cellular transformation. Through the wCDI and cell-recovery time, mechano-NPS discriminates between sub-lineages of normal primary human mammary epithelial cells. Mechano-NPS identifies mechanical phenotypes that distinguishes lineage, chronological age, and stage of malignant progression in human epithelial cells.

Visco-NPS is a new, electronic-based, microfluidic rheology platform that quantifies cellular viscoelastic properties under periodic deformation. We measure the storage (G’) and loss (G”) modulus of individual cells, which represent cellular elasticity and viscosity, respectively. By applying a wide range of deformation frequency, our platform quantifies the frequency dependency of viscoelastic properties. The measurement of G’ and G” shows that malignant breast epithelial (MCF-7) cells have distinctly different viscoelastic properties as compared to non-malignant breast epithelial (MCF-10A) cells. With its sensitivity, visco-NPS is able to dissect the individual contributions of different cytoskeletal components, i.e. actin filaments and microtubules, to whole-cell mechanical properties. Through G’ and G”, visco-NPS can also quantify the mechanical transitions—a consequence of changes in cytoskeletal organization and nucleus structure—that cells undergo as they traverse the cell cycle. visco-NPS identifies viscoelastic characteristics of cells, which can provide both a biophysical understanding of cellular behavior and a potential for clinical applications.