What are the mechanisms behind cell spreading? Chowdhury et al. decided to apply a multidisciplinary approach to this biophysical mystery.
Described in the last blog post on breast cancer mechanics, it’s clear that the extracellular matrix (ECM) is a dynamic and supportive microenvironment for cell. Cell specialisation includes flattening onto the ECM, and this is an important morphological step in determining the future of the cell’s proliferation and differentiation. If the process malfunctions, this could be the difference between life and death for the cell. The sensing mechanism behind the cell spreading and the importance of molecular tethering in the process, however, is not so clear. The researchers hypothesised that molecular tension drives cell spreading rather than molecular stiffness, a claim that has been difficult to validate because of the difficulty in decoupling these two phenomena.
Two of the researchers developed a method for defining the single molecular forces between the cell and the ECM, called the tension gauge tether. A tether such as DNA is attached to a ligand, which will join to a receptor within the cell membrane. If tension is too high, the tether will snap. This allowed the researchers to design TGTs with different tension tolerances and measure the consequential amount of cell spreading. Integrins are receptors that join the ECM outside a cell to the cytoskeleton inside the cell, and so were good candidates for measuring tension.
It was found that cell area increases in line with higher tension tolerances, and a similar amount of cell spreading was found across multiple different molecular stiffness surfaces. This finding suggests that molecular stiffness has little influence over cell spreading, while molecular tension is key.
You can read the full paper for free* using the link below:
Single molecular force across single integrins dictates cell spreading
F. Chowdhury, I.T.S. Li, B.J. L. Doğanay, R. Singh, X. Wang, J. Seong, S. Lee, S. Park, N. Wang, T. Ha
Integr. Biol., 2015, Advance Article
DOI: 10.1039/C5IB00080G, Paper
About the webwriter
Rebecca Muir is a research assistant in the Medical Sciences Division of Oxford University. Her research interests include cell biology, gender studies, philosophy of science, and mitochondrial disease. Rebecca was shortlisted for the Chemistry World’s Science Communication Competition 2015. She tweets at @rebeccalydiam and her personal website can be found on rebeccamuir.co.uk.
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