Optical micro-resonators for the study and quantification of cellular forces

Abstract

It is widely accepted that mechanical forces regulate a plethora of cellular functions, ranging from cell migration, cell differentiation and morphogenesis to cancer progression, invasion and metastasis. Changes in the mechanical phenotype of cells directly affect their biological functions. Although the importance of cell forces is undeniable, measuring these forces remains challenging in many cases but it is essential to provide a physical perspective and deepen our understanding of multiple biological processes.

In this thesis, mechanical forces at different length scales were investigated and a novel, optical approach of cellular force quantification is explored. Using resonant optics, we studied the mechanics of cancer and measured cell forces exerted by subcellular structures (invadopodia), single cells and 3D tumour spheroids. For this investigation we used a newly developed optical technique known as ERISM. Force measurements were acquired spanning from weak cancer-cell protrusions to large, supracellular stresses. Furthermore, the force dynamics of these systems were studied, showing their oscillatory nature regardless of length scale. Moreover, collective phenomena of cancer invasion were investigated, by measuring the amplitude and temporal evolution of the mechanical forces required for cancer cells to invade their environment. A force comparison between cancer and normal models has also been considered, where possible.

In addition, mechanical stresses developed in 3D multicellular environments have been imaged using deformable droplet lasers. First, droplet lasers were mechanically and optically characterised by linking a known exerted force on individual droplets with changes in resonance. Droplet lasers were then introduced into 3D tumour spheroids to sense the forces generated inside these complex structures.

The results of this thesis aim to deepen our understanding on cancer progression and invasion through a physics perspective, leading the way for novel approaches against cancer, based on mechanical cell forces.

Date of Award	1 Dec 2020
Original language	English
Awarding Institution	University of St Andrews
Supervisor	Malte Gather (Supervisor)