Degree

Doctor of Philosophy (PhD)

Department

Division of Electrical and Computer Engineering

Document Type

Dissertation

Abstract

Mechanical properties of a cell reflect its biological and pathological conditions including cellular disorders and fundamental cellular processes such as cell division and differentiation. There have been active research efforts to develop high-throughput platforms to mechanically characterize single cells. Yet, many of these research efforts are focused on suspended cells and use a flow-through configuration. Therefore, adherent cells are detached prior to the characterization, which seriously perturbs the cellular conditions. Also, methods for adherent cells are limited in their throughput.

My study is aimed to fill the technical gap in the field of single cell analysis, which is a high-throughput and non-invasive mechanical characterization of single adherent cells. I developed a multi-modal platform to mechanically characterize single adherent cells. The platform is based on optomechanical principle, which induces least perturbation on the cells and does not require cell detachment. Besides, multiple measurements can be performed on a single cell to track its mechanical behavior over time. Proposed platform can expand our understanding on the relationship between mechanical properties and cellular status of adherent cells.

Single adherent cells are characterized optomechanically using the vibration-induced phase shift (VIPS). VIPS is a phase shift of apparent velocity of a vertically vibrating substrate measured with laser Doppler vibrometer (LDV), when the measurement laser passes through an adherent cell or any transparent objects on the substrate. The VIPS and height oscillation of a single cell on a vibrating substrate have negative correlation with the cell stiffness. An analytical model is established which demonstrates relationship between cell’s mechanical properties and its VIPS.

With the VIPS measurements, at multiple frequencies on large population of cells, the statistical significant difference in the cell stiffness is confirmed after exposure to various drugs affecting cytoskeleton network. Also, a 3-dimensional finite element model is developed to extract the cell stiffness from VIPS.

VIPS technique is used to reconstruct the detailed oscillation pattern of transparent objects such as water microdroplets and intracellular lipid droplets on a vibrating substrate, which can give us better understanding of mechanical behavior of biological transparent objects.

In addition, using VIPS measurement mechanical interaction between extracellular matrixes (ECMs) and adherent cells is studied. Statistical significant difference in bonding straight of single cells and different ECMs is demonstrated.

Committee Chair

Park, Kidong

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