Cells walk further on a hard substrate
Movement of cells due to mechanical causes modelled
Cells move differently on a firm substrate than on a softer surface. Using a mathematical model, former FOM PhD researcher Elizaveta Novikova (Eindhoven University of Technology) has demonstrated for first time that there is a connection between this local behaviour of cells and their global tendency to move towards a firmer substrate. This knowledge provides starting points for specifically controlling the movement of cells. Novikova and her colleagues will published this model in Physical Review Letters on 16 February 2017.
Novikova received her doctorate last year from Eindhoven University of Technology under the supervision of Dr Kees Storm. With his group, Theory of Polymers and Soft Matter, Storm carries out theoretical research into biological systems. During a period at the University of Pennsylvania, Novikova developed a model to gain a better understanding of experimental results about the movement preferences of cells.
Cells can 'smell' and 'feel'
It has been known for a long time that the chemical environment of a cell influences its movement. Varying the concentration of a certain substance makes cells move towards either an increasing or decreasing concentration of that substance. "That probably has an evolutionary advantage. It enables cells to specifically move towards a source of nutrients or oxygen," says Storm. "That sensitivity of cells for chemical gradients can be compared to our sense of smell: cells ‘smell’ the substances in their environment and move towards or away from such substances. In a similar vein, cells have a sort of ‘tactile sense’ that is called mechanosensing in cell biology. Cells ‘feel’ the rigidity of their environment, and that influences how they move and the direction they move in."
Model
The researchers saw two effects of rigidity on cell movement stated in the literature. First, it takes longer before cells change direction on a stiffer substrate. Furthermore, when an environment varies in rigidity, the cells always move in the direction of higher rigidity. During her stay in Pennsylvania, Novikova had access to the experimental data of the group of Dennis Discher to develop her model for rigidity-driven cell movement. "Of course, this natural movement towards higher rigidity could also have an evolutionary advantage," says Storm. "However, Novikova's model reveals that the general movement towards a stiffer substrate directly arises from the local tendency of cells to move longer in a single direction on a stiffer substrate."
Directing cell movement
The model provides a new way of interpreting experimental data and of understanding how the mechanical environment can influence the movement of cells. "Moreover, this knowledge provides researchers with a new way of ‘imposing their will’ on cells by mechanically steering them or by separating different types of cells," says Storm. "That makes interesting applications outside of the body possible, such as in organs-on-chips, a new technology in which lifelike miniature organs are used for research and diagnosis outside of the body."
Since her PhD graduation, Elizaveta Novikova has worked in Paris as a post-doc at the Institut de Biologie et de Technologies de Saclay.
Contact information
Dr. Kees Storm, +31 40 247 41 17.
Reference
Title: Persistence-Driven Durotaxis: Generic, Directed Motility in Rigidity Gradients
Authors: Elizaveta A. Novikova, Matthew Raab, Dennis E. Discher, and Kees Storm
Link: http://journals.aps.org/prl/abstract/10.1103/PhysRevLett.118.078103
Reference: Phys. Rev. Lett. 118, 078103 (2016)
Doi: 10.1103/PhysRevLett.118.078103