Objetivo
In native tissues, the extracellular matrix (ECM) provides not only physical scaffolding to cells, but also biochemical and biomechanical cues affecting cell behaviour. ECM mechanical properties are critical in the regulation of cell behaviour during tissue development, homeostasis and disease via mechano-transduction. Albeit biological tissues generally exhibit a time variant (i.e. dynamic) viscoelastic behaviour that changes during development, ageing and disease, to date most of mechano-transduction studies have focused on static elastic properties only. The ENDYVE project aims at engineering tissue dynamic viscoelasticity typical of pathophysiological processes in-vivo to investigate its role on cell behaviour. Focusing on cardiomyocyte maturation, the viscoelastic properties of foetal, neonatal, aged and infarcted cardiac tissue will
be characterised and used to design cell culture substrates with temporally tuneable mechanical properties that initially mimic foetal viscoelasticity and then can be made more stiff and less viscoelastic during cell culture via a second-step biocompatible enzymatic crosslinking to recapitulate dynamic changes of cardiac viscoelasticity in-vitro. First, stem cell cardiomyocyte behaviour will be investigated at discrete levels of constant viscoelasticity by seeding human induced pluripotent stem cells on substrates prior to and after enzyme-mediated crosslinking. Then the effect of dynamic changes in
substrate viscoelasticity will be characterised during culture. Engineering dynamic viscoelasticity is a critical step towards a better understating of cell-ECM interactions and mechano-transduction, and could lead to the development of new strategies to finely control cell behaviour, with numerous potential societal and clinical implication, such as obtaining mature differentiated cells from stem cells for drug screening in vitro, or limiting, if not preventing, fibrosis and tumour progression.
Ámbito científico
- medical and health sciencesbasic medicinephysiologypathophysiology
- medical and health sciencesmedical biotechnologycells technologiesstem cells
- natural sciencesbiological sciencesbiophysics
- engineering and technologyindustrial biotechnologybiomaterials
- medical and health sciencesbasic medicinephysiologyhomeostasis
Programa(s)
Régimen de financiación
MSCA-IF-EF-ST - Standard EFCoordinador
1101 BM Amsterdam
Países Bajos
Organización definida por ella misma como pequeña y mediana empresa (pyme) en el momento de la firma del acuerdo de subvención.