Cell mechanical modeling and mechanical properties characterization

Abstract

Cell biomechanics regulate cellular physiological functions, such as locomotion, cell division, proliferation, mechanotransduction, and cell death. Current research reports that alterations of the mechanical properties of cells may be associated with the onset and progression of some diseases. Since mechanical properties are intrinsic to biological cells, they can be used as biomarkers to (1) investigate property variation, along with the developmental stages of cells; (2) distinguish normal cells from diseased ones; and (3) measure the variation of cell properties after treatment by chemicals or by varying their physiological environments. Several experimental techniques and computational approaches have been proposed to measure the mechanical responses of biological cells. However, the study of cell mechanical properties at the single cell level remains challenging. In particular, there exists an increasing need for a cell mechanical model for a variety of experimental conditions. This thesis proposes a new cell mechanical model to predict the mechanical response of cells during the process of cell manipulation and to characterize cell properties. This model is based on membrane theory and establishes the relationship between the imposed force and the induced cell deformation. Different cell properties correspond to different force-deformation curves. Therefore, by comparing the experimental data to the modeling results, the mechanical properties of cells can be characterized. By varying the boundary conditions, the proposed cell model can be applied in the following aspects. First, the proposed cell mechanical model is used to describe the deformation behavior of cells during microinjection. Based on this model, the relationship between the injection force and the cell deformation can be obtained. To verify the proposed model, microinjection experiments are performed on zebrafish embryos at different developmental stages. The experimental data correspond with the modeling results, which show that the proposed modeling methodology can be utilized to estimate the mechanical responses of cells. Moreover, the elastic moduli of zebrafish embryos are characterized, indicating embryos softening along with development before hatching. Furthermore, various constitutive materials are incorporated into the mechanical model to represent the material behavior of embryos membranes. The most appropriate material is recognized for a specific biomembrane when the best fitness between the experimental and modeling results is achieved. Second, optical tweezers technology is utilized to study the effect of osmotic condition on the cell properties of human red blood cells (RBCs). The trapping forces and the cell deformations are obtained through force calibration and image processing, respectively. To extract the mechanical properties of RBCs, the cell mechanical model is extended for spherical RBCs, and finite element (FE) analysis is conducted for biconcave RBCs. Based on the cell modeling methods, shear moduli of RBCs in different osmotic conditions are characterized, revealing an increase of cell stiffness with increasing osmolality. Third, the proposed mechanical model is applied to predict the deformation responses of RBCs when stretched by two counter-propagating laser beams in an optical stretcher. Comparison with the experiments reported in the literature reveals that the modeling results agree with the experimental data, which in turn demonstrates the validity of our developed model. Furthermore, the mechanical properties of RBCs are obtained. This study demonstrates that our mechanical model can be used to predict the deformation response and characterize the cell mechanics of RBCs in the optical stretcher.

Date of Award	15 Jul 2010
Original language	English
Awarding Institution	City University of Hong Kong
Supervisor	Dong SUN (Supervisor)