All Subdomains of the Talin Rod Are Mechanically Vulnerable and May Contribute To Cellular Mechanosensing

Significance Statement

Integrin-mediated adhesions have been a vital area of research in mechanotransduction. Integrins are known to provide a stable link between the extra cellular matrix and the cytoskeleton to facilitate mechanosensing, force generation and motility among many other processes. Integrins are also an integral part of focal adhesions, which are clusters of intracellular proteins that allow the bidirectional mechanical communication of cells with their surroundings..

Talin, is one of the main proteins in these integrin based focal adhesion complexes, and is essential for cellular spreading and to connect integrins with the actin cytoskeleton. Previous studies had showed that the N-terminal sub-region of the talin rod comprising the bundles R1-R3 increases the number of vinculin molecules (another key focal adhesion protein) bound to the talin molecule after force-induced stretching of this region. The fact that this region contains almost half of the vinculin binding sites of the entire talin rod led to the hypothesis that this region was the mechanosensitive part of the talin molecule, while the rest of the talin rod was responsible for force propagation.. However, the response of the remaining linear region to force has not been studied.

Recently, a collaborative effort from two research teams based at Imperial College London in the UK, and The University of Tampere in Finland have combined cutting edge single molecule atomic force microscopy (smAFM) and different cloning engineering strategies with steered molecular dynamics SMD simulations to demonstrate that indeed all domains of the talin rod can act as mechanosensors in cells, as all of them unfold over a physiological range of forces between 10 and 40 pN. The work published in the prestigious journal ACS Nano in an open access format that can be download from ( opens new horizons for further studies that elucidate how the unfolding of the different regions of the talin rod molecule can affect precise sub-cellular and molecular mechanisms

Talin is a crucial molecule in cell mechanics and understanding how its unfolding may affect its interaction with other proteins and furthermore determine the cell fate by triggering alternative downstream singalling is of fundamental relevance to understand how mechanical forces combine with biochemical signaling to produce an overall cellular response. Without knowing the intricacies of the processes by which cells manage mechanical forces, our knowledge of cell behavior would be limited.

This research study showed clear understanding of principles and mechanisms of talin-mediated mechanotransduction which may provide crucial insights into the biological study health and diseases.


All Subdomains of the Talin Rod Are Mechanically Vulnerable and May Contribute To Cellular Mechanosensing. Advances in Engineering

About the author

William Haining is a PhD student in the Cellular and Molecular Biomechanics Laboratory at Imperial College London. He studied Natural Sciences, specialising in Physics, as an undergraduate at the University of Cambridge. Following this, he received his masters from Columbia University in Biomedical Engineering.

His interests lie at the interface between cell biology and physics, combining cutting edge molecular techniques such as single-molecule atomic force microscopy with the latest advances in cellular imaging and analysis. 

About the author

Magdaléna von Essen is a  PhD student in multidisciplinary Protein Dynamics research group in BioMediTech at the University of Tampere, Tampere, Finland. She studied pharmacy as an undergraduate at the Veterinary and Pharmaceutical University in Brno, Czech Republic. She received her Msc in Bioinformatics from the University of Tampere, Finland.

In her work she focuses on the connection between protein functional mutations and cell biology in health and disease using computational molecular modeling and simulation methods.  

About the author

Associate Professor Vesa P. Hytönen is a leader of multidisciplinary Protein Dynamics research group in BioMediTech at the University of Tampere, Tampere, Finland. After graduating as a PhD from the University of Jyväskylä, Jyväskylä, Finland at 2005, he conducted postdoctoral training at ETH Zurich, Zürich, Switzerland 2005–2007. He then continued as a postdoctoral researcher at the University of Tampere and established independent research group at 2010.

His research interests are mechanobiology, protein engineering and vaccine research and he has authored more than 100 peer-reviewed original scientific articles. 

About the author

Dr. Armando del Río Hernández obtained his PhD in Chemistry from the Computense University in Madrid. Following this, he completed a period of postdoctoral training in the US. He worked at Columbia University of New York as a Research Fellow first, and as a Research Associate (equivalent to Research Assistant Professor), later. His research in the field of mechanotransduction showed how mechanical forces can unfold protein domains to expose cryptic sites, and to trigger downstream signaling pathways.

Dr. del Río Hernández currently leads the Cellular and Molecular Biomechanics group in the Department of Bioengineering at Imperial College London ( This is a multidisciplinary team that combines nanotechnology, and celular molecular biology tools with biophysical and bioengineering approaches to investigate how mechanical stimuli regulate the behaviour of cells and molecules in physiological conditions and in cancer.  

Journal Reference

Alexander William M. Haining1, Magdaléna von Essen2,3, Simon J. Attwood1, Vesa P. Hytönen*2,3, Armando del Río Hernández*1. All Subdomains of the Talin Rod Are Mechanically Vulnerable and May Contribute To Cellular Mechanosensing.  ACS Nano, 2016, 10 (7), pp 6648–6658.

Show Affiliations
  1. Cellular and Molecular Biomechanics Laboratory, Department of Bioengineering, Imperial College London, London SW7 2AZ, United Kingdom.
  2. BioMediTech, University of Tampere, Biokatu 6, FI-33520 Tampere, Finland.
  3. Fimlab Laboratories, Biokatu 4, FI-33520 Tampere,Finland.



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