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Mechanobiology

 

Extracellular matrix mechanosensing

Cells are able to detect external force and some of them developed as mechanosensitive cells. One such example are the hair cells of the inner ear. These cells are deflected by the vibration caused by sound and acceleration and transmit signal to the brain that will be interpreted as sound or movement. However, cells can also apply forces to the external environment they inhabit which is the extracellular matrix (ECM). By pulling the ECM cells can fell how soft or hard a material is and this determine how they move, grow and differentiate.

We have published a book chapter where we discussed the importance of mechanosensing in medicine.

We wrote a paper on how groups of cells can feel through materials – a very important consideration for healing and development of organs.

We found that by acting as groups, cells can feel much further than they can when acting alone - 16 times further in fact! By using time-lapse imaging to ‘speed up’ cell movement, we could see in the videos large cell groups moving, contracting and deforming the material more than single cells.

In another video, it can be seen how the deformations extended greater distances from the periphery of colonies on thick hydrogels than on thin ones.

 

Colonies of cells similar in size produce more displacement on thick hydrogels than on thin ones.

Finally we conclude that that groups of cells are able to feel deeply into materials, rather like the proverbial “princess and the pea”. This finding may be very relevant for the design of implants to help cure disease, for understanding how cancer progresses or to understand the way our body heals and develops.

Groups of cells are able to feel deeply into materials, like the proverbial “princess and the pea”.

A better understanding of ECM mechanosensing may have exiting consequences in wound healing and embryogenesis. This may lead to the development of a new wound healing treatment, which will take in consideration the mechanical properties of the wound bed. Exploiting the potential of embryonic stem cells could provide potential ways of using them in regenerative medicine by modulating the mechanical properties on the material they are attached. Nevertheless, a better understanding of ECM role in cell growth and migration will lead to the development of biomaterials for tissue engineering.

 

During development and wound healing, tissues rapidly change in size, shape, composition, and in their mechanical characteristics. Cells within these tissues - which are of course responsible for making these tissues in the first place! - are exposed to a variety of forces, including tension, compression and shear, as well as the static mechanical properties of the stuff they grow on (other cells and 'extracellular matrix'). It's now widely appreciated that cells can feel and respond to these forces by moving, growing and differentiating.

 

We are now investigating how the mechanical characteristics of the growth environment direct cells how to behave in processes involved in wound healing and tissue regeneration. We hope that our results might give us a better understanding of how to promote improved regeneration and healing following injury.