Cell mechanics study on single cell and collective behavior

• Main Author: Han, Jingjing
• Other Authors: Chew Lock Yue
• Format: Theses and Dissertations
• Language: English
• Published: 2017
• Subjects: DRNTU::Science::Chemistry::Biochemistry
• Online Access: http://hdl.handle.net/10356/70071
• Institution: Nanyang Technological University

The investigation of cell-cell and cell-substrate interactions from the perspective of physics is fundamental to the study of cell mechanics. Based on the fact that cells are exposed to various biochemical as well as mechanical cues from their environment, we have conducted research on the influence of these cues on their biomechanical behaviors. Specifically, we focus on single cell contraction and cells' collective motion in the space of 2-dimensional, and single cell morphology study in the space of 3-dimensional. Fibronectin and collagen type I are extracellular matrix proteins that play important role in the modulation of cell mechanics and other physiological processes such as angiogenic sprouting. In the first project, we have conducted comparative analyses of cell contraction on fibronectin and collagen. Our study has found that during the early stage of cell spreading, human umbilical vein endothelial cells (HUVECs) exhibit stronger and more directed contraction on fibronectin than collagen type I coated microposts. In Particular, greater cell traction force, larger spreading area, and higher directionality are all observed in microposts coated with fibronectin. In addition to being regulated by biochemical signals transmitted through various molecules, cellular functions also depend on the mechanical properties of the substrate like its nanotopography. Meanwhile, the coordination among cells is important in maintaining the integrity of group behavior during collective cell migration. The key question we investigate in the second project is on the influence of the substrate property of roughness on collective cell migration. Through our experimental investigation and analysis, we have uncovered that cells tend to display a slower and less directional collective migration on nanoroughened substrate. Moreover, the expression of adhesion proteins is also observed to decrease on a rough substrate. Currently, there are various in-vitro studies of cell morphology in 2D, but this does not represent the more physiological profile of in-vivo cells. Hence, in the third project, we have initiated a study on cell attachments in 3D nanoroughened scaffold to mimic the in-vivo cellular environment. Our objective is to investigate how matrix nanotopography impact cell function in 3D relative to 2D. We found that cells exhibit distinct adhesions with different number of focal adhesions between a smooth scaffold and a rough scaffold with nano-spikes. More importantly, our analysis on cell surface curvatures indicates significant correlation between the distribution of cortical actin and the local curvature of cell surface. In summary, our studies have provided insights into the physics of cellular mechanics through the complex interactions of a single cell or a collection of cells with the biochemical and mechanical cues of the environment. I believe this thesis had brought us closer to a deeper understanding on the mechanical behavior of cells with potential application in the design of biomedical devices for the purpose of cellular manipulation.