The challenges of studying mechanical properties in cells

Shape, volume, pressure, tension, stiffness, force, viscoelasticity, adhesion, flow…  All these mechanical properties directly affect our tissues, cells, and cellular components. Cells, for instance, can feel how rigid their underlying surface is, how their membrane stretches or compresses, or how much pressure other structures exert on them. They then convert these physical forces and mechanical properties into biochemical signals, triggering different effects and behaviors that cause the cell to reshape, deform, or migrate to a different location, among others.  

At the moment, mechanobiology – the field that studies how biological components sense, interpret, and convert mechanical features into biochemical signals – is facing several challenges. Firstly, measuring mechanical properties from the molecular to the cellular level requires high precision in both space and time, covering everything from the sub-nanometer to the centimeter regime and from microseconds to days; a versatility that current tools have not yet achieved. Secondly, tools to manipulate and apply these mechanical stimuli at defined magnitudes, locations, times, and rates are also lacking, as well as reference systems to accurately calibrate them. Finally, understanding how different mechanical parameters affect each other and how they interact with other biological and physiological parameters is essential for building accurate theoretical frameworks. Current models, in contrast, tend to oversimplify and typically lead to discrepancies when interpreting the results.

All these challenges have now been comprehensively presented in a Nature Nanotechnology perspective article, co-led by ICFO Prof. Michael Krieg. The article combines the efforts of several experts in mechanobiology from institutions across the globe, including the ETH Zürich, the University of California, the Institute for Bioengineering of Catalonia (IBEC), the Institute of Human Biology (IHB), the Friedrich Miescher Institute for Biomedical Research (FMI), the Max-Planck-Institute for the Physics of Complex Systems, the Center for Systems Biology Dresden, PSL University, the Swiss Institute of Bioinformatics, the École Polytechnique Fédérale de Lausanne (EPFL), the University of Basel, and the University of Glasgow.

Together, the team has identified the key aspects that must be systematically tackled in order to deepen our understanding of the mechanical attributes of biological samples. “We believe that our insights can guide future research in mechanobiology, helping us decipher how complex cellular systems sense, respond to, and apply mechanical cues,” says Prof. at ICFO Michael Krieg, one of the first co-authors of the article. “To do so, changing our approach from reductionistic to holistic is key,” he stresses. According to the authors, successfully addressing the presented challenges could, in turn, lead to significant improvements in several biotechnological and medical applications.

Reference:

Kashuba et al. Advancing mechanobiology from single molecules to complex cellular systems. Nature Nanotechnology, 2026.

DOI: https://doi.org/10.1038/s41565-026-02179-0

Acknowledgements:

We acknowledge funding from the Swiss National Science Foundation (SNFS, grant numbers 31003A_182587/1 to D.J.M.,315230_219990 to D.I. and P500PB_225505 to K.C.K.), the SNFS as part of the NCCR Molecular Systems Engineering (grant number 51NF40-205608) and the Marie Sklodowska Curie Actions (grant number 101206469). M.K. acknowledges MCIN/AEI/10.13039/501100011033/FEDER “A way to make Europe” (PID2024-157334OB-I00), “Severo Ochoa” programme for Centres of Excellence in R\&D (CEX2019-000910-S), from Fundació Privada Cellex, Fundació Mir-Puig and from Generalitat de Catalunya through the CERCA and Research programme.