Cell’s elasticity is an integrative parameter summarizing the biophysical outcome of many known and unknown cellular processes. This includes intracellular signalling, cytoskeletal activity, changes of cell volume and morphology and many others. Not only intracellular processes defines a cell`s elasticity but also environmental factors like their biochemical and biophysical surrounding. Cell mechanics represents a comprehensive variable of life. A cell in its standard conditions shows variabilities of biochemical and biophysical processes resulting in a certain range of cell’s elasticity. Changes of the standard conditions, endogenously or exogenously induced, are frequently paralleled by changes of cell elasticity. Therefore cell elasticity could serve as parameter to characterize different states of a cell.The interactom of a cell (the functional network of a cell consisting of genome and proteome) is constantly influenced by mechanical forces and activates downstream cellular mechanosresponse.
Biomechanical properties of living cellsElasticity <-> Viscoelasticity <-> Stiffness
In literature the biophysical property of a cell is reported as elasticity (elastic modulus), viscoelasticity and stiffness. Although all parameters provide information about the resistance of a material to deformation (the amount of deformation is called the strain), they show significant differences.
- A material is said to be elastic, if it will deform under stress (e.g., external forces) and will return to its original shape when the stress is removed. The relationship between stress and strain (force – deformation) is linear and the deformation energy is returned completely. Elasticity is often referred to as the Young's modulus (E).
- Viscoelasticity is the property of materials that exhibit both viscous and elastic characteristics when undergoing deformation. Viscosity is a measure of the resistance of a fluid to being deformed by either shear stress or extensional stress. It is the result of the diffusion and interaction of molecules inside of an amorphous material. The reciprocal of viscosity is fluidity. The relationship between stress and strain is non-linear for viscoelastic material and the deformation energy is not returned completely. The amount of this lost energy is represented by the hysteresis of a loading and unloading cycle (hysteresis in the force-deformation curve).
- Stiffness is the resistance of a solid body to deformation by an applied force. In general, elastic modulus is not the same as stiffness. Elastic modulus is a property of the constituent material; stiffness is a property of a solid body. The elastic modulus is an intensive property (does not depend on the size, shape, amount of material and boundary conditions) of the material; stiffness, on the other hand, is an extensive property (depends on the size, shape, amount of material and boundary conditions) of the solid body. An example: a solid block and a soft flat spring made from the same material (e.g. steel) show the same elastic modulus but a different stiffness.
AFM-based mechanical measurements of cell mechanicsThe principle of an elasticity measurement is to physically indent a cell with a probe, to measure the applied force and to process this force-indentation data using an appropriate model. This allows a calculation of the components of stress and deformation and gives a relation for elasticity, loading force, indentation and Young's modulus. The unit of the Young`s modulus (E) is the pascal (Pa).
Atomic force microscopy (AFM) combines high spatial resolution with very high force sensitivity and allows investigating mechanical properties of living cells under physiological conditions. However, elastic moduli reported in the literature showed a large variability, sometimes by an order of magnitude (or even more) for the same cell type assessed in different labs. Clearly, a prerequisite for the use of cell elasticity to describe the actual cell status is a standardized procedure that allows obtaining comparable values of a cell independent from the instrument, from the lab and operator.
Schillers H. Measuring the Elastic Properties of Living Cells. Methods Mol Biol. 2019;1886:291-313. doi: 10.1007/978-1-4939-8894-5_17. PMID: 30374875.
An European approach to standardize cell elasticity measurements
Biologically derived variations of elasticity cannot be reduced due to the nature of living cells but technically and methodologically derived variations could be minimized. Within a European network, we developed a standardized procedure of AFM-based elasticity measurements to achieve high precision and high reproducibility on living cells measurements.