ENDYVE · ENgineering DYnamic ViscoElasticity to study cell response
Horizon 2020 — Marie Skłodowska-Curie Actions
- Duration
- 2016-11-01 → 2018-06-30
- EU contribution
- €137,999
- Participants
- 1
- Scheme
- MSCA-IF
Lines connect the coordinator with its partners.
Results in brief
ENgineering DYnamic ViscoElasticity to study cell response
The biomechanical properties of the extracellular matrix (ECM) play critical roles in directing pathophysiological cell behaviour via mechano-transduction. Although biological tissues generally exhibit a viscoelastic behaviour that changes over time during development, ageing and disease (here named dynamic viscoelasticity), the majority of mechanobiology studies have focused only on static (i.e. time-invariant) mechanical properties, typically by characterizing tissue elasticity and investigating cell behaviour as a function of substrate stiffness. With the ultimate goal of contributing to a better understanding of pathophysiological cell mechano-transduction mechanisms, the ENDYVE project was aimed at engineering the dynamic viscoelasticity typical of tissue pathophysiological processes in-vivo to start exploring its role in the modulation of stem cell behaviour. This can have a number of societal and clinical implications, such as developing new strategies to control stem cell behaviour for obtaining mature differentiated cells for drug screening in-vitro, or limiting, if not preventing, tissue fibrosis and tumour progression in-vivo. Focusing on cardiac development and pathophysiology, the project goals were achieved through a series of multi-disciplinary activities divided into 4 work packages (WPs), outlined in the next section. Complementary project-related studies were also carried out to: -Develop of a new analytical method for estimating lumped parameter constants of linear viscoelastic models from strain rate tests; -Compare frequency and strain-rate domain mechanical characterization; -Analyse intimal, medial and adventitial stiffness in human aneurysmal abdominal aortas.
Data: CORDIS, © European Union
Project objective
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 willbe 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 insubstrate 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.
Original text from CORDIS.
Participants
- OPTICS11 B.V. · AMSTERDAMCoordinatorNetherlands
Links
- View on CORDIS
- DOI: 10.3030/705296
- https://www.researchgate.net/project/ENgineering-DYnamic-ViscoElasticity-to-study-cell-response-ENDYVE
Data: CORDIS, © European Union