Investigation of mechanical biology of cells by using tension sensors and magnetic tweezers

Abstract

Cancer metastasis remains to be one of the most important research areas due to their high fatal rate. Recent reports have drawn the attention of mechanotransduction in cancer metastasis. Mechanotransduction is the process where cells receive mechanical stimuli from their extracellular matrix or from connecting cells. The received physical signals can be transformed into biochemical signals which might contribute to affect cell metabolism and migration. In this thesis, I first described a high-force magnetic tweezers developed in our lab to measure the mechanical properties of living cells. Then, our observation of mechanical interplay between the external substrates and living cells through focal adhesions was explained. Finally, the crosstalk between cell-ECM connections through focal adhesions and cell-cell connections through adherens junctions were discussed. The developed high-force magnetic tweezers can be used for applying force larger than 20 nN to living cells. Integrated magnetic tweezers and fluorescence microscopy enables us to measure force application and tension in mechanosensitive proteins at the same time. By changing the stiffness of the underlying substrates, we found that MDA-MB-231 cells (metastatic breast cancer cells), can tune their rheological properties and tension in focal adhesions on substrates with varying stiffness. MDA-MB-231 cells became more elastic on more rigid substrates. Higher tension was detected in MDA-MB-231 cells by using talin tension sensors when they grow on stiffer substrates. In contrast, MCF-10A cells (normal breast cells), lack this adaptive capacity against the substrate of varying stiffness. Furthermore, the correlation between focal adhesions and adherens junctions in MDCK cells was detected. By stretching the focal adhesions through magnetic tweezers, tension in cadherins increased once after the force application. Our results showed confirmed the ability of cancer cells to sense the external mechanical stimuli and change their mechanical properties accordingly.

Date of Award	2020
Original language	English
Awarding Institution	The Hong Kong University of Science and Technology
Supervisor	Hyo Keun PARK (Supervisor)