Spatial Distribution of Filament Elasticity Determines the Migratory Behavior of a Cell

• Main Authors: Hans I-ChenHarn, 韓逸成
• Other Authors: Ming-Jer Tang
• Format: Others
• Language: en_US
• Published: 2015
• Online Access: http://ndltd.ncl.edu.tw/handle/98271217079583954006

博士 === 國立成功大學 === 基礎醫學研究所 === 103 === The mechanical properties of a cell is tightly regulated by multiple facets of intracellular processes and external factors. Any cellular response leading to morphological changes is highly tuned to balance the force generated from structural organization, provided by the cytoskeleton. Actin filaments serve as the backbone of intracellular force, and transduce external mechanical signal via focal adhesion complex into the cell. During migration, cells not only undergo molecular changes but also rapid mechanical modulation. Furthermore, how are the force and filament elasticity spatially regulated in different migratory behavior still remain unclear. These questions require advances in measuring devices to explore the biomechanical properties of biological samples from tissue to cellular and sub-cellular level. In the introduction, I reviewed the cutting edge technologies used today to measure biological samples on tissue and cellular levels, the mechanotransduction of different organ systems and the cell, the role of different cytoskeletons in the mechanobiology of the cell, and the cytoskeletal dynamics of cell migration. In chapter 3, I established a measuring methodology using atomic force microscopy to show 1) non-migratory cells only generated one type of filament elasticity, 2) cells generating spatially distributed two types of filament elasticity showed directional migration, and 3) pathologic cells that autonomously generated two types of filament elasticity without spatial distribution were actively migrating non-directionally. In chapter 4, I extended this model and explored the migrating nature of keloid fibroblasts, in which the coupling of filament elasticity and force generation through focal adhesion kinase play a vital role. The dissertation provides a whole new perspective to the elasticity of actin filaments, and how they are differentiated in different modes of migratory behavior.