Thesis
Optimisation of nanovibrational stimulation to control the mechanical properties and differentiation of adult stem cells
- Creator
- Rights statement
- Awarding institution
- University of Strathclyde
- Date of award
- 2025
- Thesis identifier
- T17258
- Person Identifier (Local)
- 202060628
- Qualification Level
- Qualification Name
- Department, School or Faculty
- Abstract
- Interdisciplinary science has become more common in recent years, with fields such as mechanobiology exploring the interconnection between biology and engineering to focus on how mechanical forces influence cell behaviour and tissue function. Understanding how cells sense and respond to their environment is key to understand a range of diseases such as cancer, cardiovascular disorders, and musculoskeletal conditions. In stem cells, understanding their mechanobiology and controlling their differentiation is essential when designing cell therapies. Mechanical stimulation has been widely used to induce a response in cells, using techniques such as cyclic stretch, compression, and fluid shear stress. Vibrational stimulation is another method and has the potential to be used to engineer cells for therapeutic use in vitro, or to be used directly on patients through wearable devices. However, studies have vastly differed on the optimal vibration conditions to induce specific cell responses. This has made it challenging to understand precisely which parameters optimise a desired response. Nanovibrational stimulation, a technique previously conceptualised by Prof. Adam Curtis applies nanoamplitude vibrations to cells in an attempt to induce a response by targeting motion at the protein length scale. It has previously successfully induced osteogenic responses in stem cells, as well as being used in other applications such as reducing biofilm formation in Pseudomonas aeruginosa biofilms. However, a full study into the optimisation of nanovibrational stimulation has never been done. This thesis aimed to explore the effect of different vibration conditions on cells in an attempt to enhance cell response to mechanical stimulation. Four vibration parameters were explored: frequency and amplitude of vibration, duration of stimulation and the direction of the applied force. Four cell types were also investigated: murine fibroblasts cells (NIH 3T3s), human osteosarcoma cells (MG63s), human neuroblastoma cells (SH-SY5Y) and human mesenchymal stem cells (MSCs). We present data investigating the relationship between the mechanical, morphological and gene expression response in cells, identifying an initial increase in the stiffness of cells following the application of vibration. In fibroblasts, this corresponded with an increased nuclear area and increased actin intensity, demonstrating for the first time, the relationship between mechanical and morphological changes in cells exposed to nanovibrational stimulation. Here, we also developed a new nanovibration device capable of applying horizontal vibration to cells at a frequency of 1 kHz and up to 100 nm in amplitude. Experiments conducted on MG63 cells, with horizontal vibration at a higher amplitude resulted in an increased response in cells. When applied to MSCs, some cell responses were indeed increased compared to cells vibrated vertically at 1 kHz, 30 nm. Finally, we also present data using three mesenchymal stem cell (MSC) donors testing the donor response to vibrational stimulation. The varied response across all three donors highlights the need to optimise vibration parameters for different donor ages, genders, and potentially ethnicities, which must be explored further before nanovibrational stimulation may be used for cell therapies or as wearable devices
- Advisor / supervisor
- Childs, Peter
- Resource Type
- DOI
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PDF of thesis T17258 | 2025-05-29 | Public | Download |