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Study of mechanical properties and cyclic stretching-induced remodeling of cellular primary cilia
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| Title: | Study of mechanical properties and cyclic stretching-induced remodeling of cellular primary cilia |
| Other Titles: | 細胞一次繊毛の力学特性と繰り返し引張刺激に伴うリモデリングに関する研究 |
| Authors: | DO, Dung Tien Browse this author |
| Issue Date: | 26-Sep-2022 |
| Publisher: | Hokkaido University |
| Abstract: | The primary cilia are solitary, immotile organelles that project from the surface of almost every cell in human body. They function as mechanosensors, which help cells to sense surrounding mechanical signals such as fluid flow shear stress, and then adapt to the change of mechanical stimulation. Understanding the mechanical properties of primary cilia provides better insight into how primary cilia respond to applied mechanical signals. However, the mechanical properties of primary cilium are still not well-understood, especially the elastic and viscoelastic properties. Moreover, although the responses of primary cilia to fluid flow have been well studied, the remodeling of primary cilia in response to indirect stimulation such as substrate stretching is a mystery. In this dissertation, the mechanical properties of primary cilia were elucidated, such as Young’s modulus and viscoelastic properties, together with the remodeling of primary cilia in response to cyclic substrate stretching. In addition, the microstructures of primary cilia were studied to get a better understanding of cilia mechanical responses and mechanotransduction function. A primary cilium model, including the major mechanical components, was also simulated.
In Chapter 1, the fundamentals of cells and primary cilia (their structures and functions in cell life) were reviewed. The prior studies of measurement of mechanical properties of cilia and remodeling function in response to mechanical forces were described. This chapter also reviewed the methodologies of mechanical testing and mechanical loading applied to biological materials.
In Chapter 2, the in-house micro-tensile experiment set-up and related components supporting the investigation of mechanical properties of primary cilia were introduced. The primary cilia were isolated from cells and executed by the micro-tensile experiments to obtain the Young’s modulus at different strain rates. The viscoelastic models of primary cilia were mathematically built up and the global fitting with experimental data was run to induce viscoelastic properties of primary cilia. As far as we know, this study is the first direct measurement of Young’s modulus and viscoelasticity of primary cilia. Moreover, together with global Young’s modulus, the distribution of local Young’s modulus on the primary cilia by the Atomic Force Microscope (AFM) was provided for comparison.
In Chapter 3, the remodeling function of primary cilia in response to the cyclic substrate stretching and the microstructures of primary cilia contributing to their mechanics was investigated. While the direct stimulation of fluid flow to primary cilia is well-known, the indirect stimulation of cyclic substrate stretching to primary cilia is still not characterized. It was revealed that primary cilia may adapt and remodel their behaviours (length, incidence, orientation) in response to cyclic substrate stretching. Our first tests suggested biologically that the actin cytoskeleton network contributes to transmit the mechanical signal from the substrate to the primary cilium.
Chapter 4 showed the microstructure components of primary cilia using Transmission Electron Microscopy (TEM), which provides a better understanding of responses of primary cilia to mechanical signals. The TEM images showed visually the connection of the base of primary cilia to the actin filaments supporting the hypothesis in Chapter 3 that actin network is an intermediate factor transmitting mechanical signals from the substrate to cilia. In addition, the numerical results in this chapter illustrate for the first time a primary cilium model, including the main mechanical components of cilia: microtubules and cross-linking structure. Most of the previous studies assumed the primary cilium as a homogenous and elastic beam; this model may help further cilia simulation to obtain a better understanding of cilia mechanics.
Chapter 5 summarized the works in the dissertation and offers the prospective studies that can be investigated in this research field. |
| Conffering University: | 北海道大学 |
| Degree Report Number: | 甲第15178号 |
| Degree Level: | 博士 |
| Degree Discipline: | 工学 |
| Examination Committee Members: | (主査) 教授 大橋 俊朗, 教授 梶原 逸朗, 教授 東藤 正浩, 教授 清水 裕樹 |
| Degree Affiliation: | 工学院(人間機械システムデザイン専攻) |
| Type: | theses (doctoral) |
| URI: | http://hdl.handle.net/2115/87185 |
| Appears in Collections: | 学位論文 (Theses) > 博士 （工学）
課程博士 (Doctorate by way of Advanced Course) > 工学院(Graduate School of Engineering)
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