The mechanical properties of the extracellular matrix (ECM) have emerged as critical regulators of tissue behaviour in a myriad of diverse processes that expand from morphogenesis to cancer. From the mechanical properties of the ECM, elasticity has attracted most efforts as the main regulator of tissue function. The elasticity of the ECM is generally characterized by its stiffness, which is the stress (force per unit area) needed to induce a given strain (deformation). Increased stiffness is a hallmark of most cancers as cells acquire a malignant phenotype when seeded above their physiological stiffness, tumours are generally stiffer than surrounding tissues8 and tumour stiffness is a property used for medical diagnosis simply by tissue palpation or by imaging techniques. Beyond cancer, elasticity controls processes during development (i.e. differentiation, proliferation, or morphogenesis) and wound healing. Research in this space operates under the assumption that tissues are purely elastic. Purely elastic solid materials immediately deform when they are submitted to a force, maintain a constant deformation as long as the force is held constant and immediately return to their original shape when the force deforming them is removed. However, tissues are not merely elastic but both elastic and viscous (viscoelastic). Contrary to elastic materials, viscous liquid materials’ strain is not instantaneous, and they continuously deform with time under force in an irreversible manner. Biological tissues exhibit a first instantaneous solid elastic response followed by a time-dependent liquid viscous behaviour where forces are dissipated, and stresses are relaxed. The viscoelastic response affects all tissues regardless of their stiffness (i.e. muscle, breast, bone, brain, adipose tissue, liver). The viscoelastic nature of the ECM is starting to emerge as a pivotal determinant of cellular responses. We hypothesize that the viscoelastic properties of the ECM provides a novel fundamental mechanosensitive pathway that control tissue function and works with or overrules elastic responses. The objective of VISCOMATRIX is to understand which are the mechanisms that cells use to sense the properties of 3D viscoelastic ECMs and how these regulate tissue homeostasis and malignant transformation.
VISCOMATRIX is focused on a highly relevant system which is the mammary gland and related mammary tumours. This choice is based on: (i) First, breast tumour impacts approximately 1 in 8 women. ii) Second, breast mammary gland is a viscoelastic tissue. (iii) Third, even if the role of viscoelasticity is unknown, it is well known that mammary gland and tumour development is associated with strong changes in mechanical properties. Our preliminary results show that viscoelasticity significantly affects tissue function. Therefore, as all tissues are viscoelastic, the biomedical impact of the importance of viscoelasticity is expected to be dramatic and impact fields ranging from regenerative medicine to cancer, and fibrosis. In the bioengineering filed, we believe that our findings will affect biomaterial development as well as the development of new imaging techniques to determine the viscoelastic properties of tissues. As to cancer, clinical trials targeting matrix metalloproteinases or integrins have been so far disappointing. The inclusion of viscoelasticity in the equation may provide crucial information to progress disease treatment and develop drugs.
