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Developing force measurement techniques for cell mechanics and contractility in ageing dermal fibroblasts

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Yu, Zhuonan (2021) Developing force measurement techniques for cell mechanics and contractility in ageing dermal fibroblasts. PhD thesis, University of Warwick.

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Abstract

Cellular contraction force plays a crucial role in the normal function of a biological cell. Such importance is greatly enhanced in dermal fibroblasts' function as contraction force generation is directly related to fibroblast's ability in migration and the maintenance of the extracellular matrix. In other words, the contractility of dermal fibroblasts has a close link to the physiological function of the skin as a physical barrier and regulatory organ for the homeostasis of the human body. Despite the fact that the ageing-associated changes in dermal tissue have been studied extensively, there remains a paucity in quantitatively characterising the contractility changes of dermal fibroblasts as an effect of ageing.

The primary goal of this research project is to develop a viable technique in differentiating the contraction force generated by young and aged dermal fibroblasts, which are both highly quantitative and cell-friendly. A novel nano-biomechanical technique has been developed to measure the contraction force exerted by dermal fibroblasts embedded in collagen hydrogels. The collagen hydrogel provides cells with a 3D matrix that mimics physiological conditions in the native tissue, which can be further modified by the residing cells, promoting natural behaviours of the cells. The technique can estimate the contraction force of the embedded cells over a given culture time (up to 48 hours) by accurately measuring the elasticity and the geometrical change of the hydrogel disk. A tailored indentation tester system achieves the measurements in combination with mathematical modelling based on material properties and contact mechanics. The model is further verified by finite element analysis in the prediction of force-displacement of the gel under indentation. The bio-nano-biomechanical tester developed in the project has resolutions of 10 nN and 100 nm in force and displacement, respectively, and can be used in characterising the mechanical behaviours of other soft biological tissues and biomaterials.

The novel technique was applied to measure the contraction force of dermal fibroblasts derived from `young' (< 30 years old) and `aged' (> 60 years old) donors and transforming growth factor β1 was used as agonist to stimulate contraction. Aged cells showed larger basal contractility while young donors responded to stimulation significantly more. The nano-biomechanical technique demonstrated its ability to differentiate the contraction force of young and aged dermal fibroblasts and the potential of extending the technique further into the study of cell mechanics.

Item Type: Thesis or Dissertation (PhD)
Subjects: Q Science > QH Natural history
Q Science > QP Physiology
Library of Congress Subject Headings (LCSH): Cell physiology, Cells -- Contraction, Cells -- Aging, Fibroblasts, Colloids
Official Date: February 2021
Dates:
DateEvent
February 2021UNSPECIFIED
Institution: University of Warwick
Theses Department: School of Engineering
Thesis Type: PhD
Publication Status: Unpublished
Supervisor(s)/Advisor: Liu, Kuo-Kang
Sponsors: University of Warwick. School of Engineering
Format of File: pdf
Extent: xvi, 157 leaves : illustrations
Language: eng

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