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H2020Staff exchange2015–2019

MATRIXASSAY · Novel Cell Migration Assay Based on Microtissue Technology and Tissue-Specific Matrices

Horizon 2020 — Marie Skłodowska-Curie Actions

Duration
2015-06-01 → 2019-05-31
EU contribution
€931,500
Participants
10
Scheme
MSCA-RISE

Lines connect the coordinator with its partners.

Results in brief

Novel Cell Migration Assay Based on Microtissue Technology and Tissue-Specific Matrices

Most migration assays operate based on a migration zone created when a stopper is removed or a scratch is made. Both of these methods can damage the underlying tissue-specific ECM, which is critical to the proliferation and migration of the cells and therefore to the reliability and accuracy of the assay. With the foregoing in mind, the overall scientific objective of our project is the development of a novel assay, where instead of using a gap, a size-specific microtissue containing a known number of cells is placed on a tissue-specific ECM. Briefly, the project aims to exchange knowledge and skills in the areas of assembly and characterisation of functional biomaterials, mathematical modelling of mechanical properties of biomaterials and layered scaffolds and their measurement, the formation of organotypic microtissues, and the migration of cells on aligned substrates in response to well-characterised tuneable mechanical and structural properties, which will lead to the development of a novel prototype cell migration and invasion assay that offers significant advantages over existing assays. Objectives: 1) Determine experimentally the structure-property relationships between collagen I matrices with controlled thicknesses and fibril diameter and alignment, and their mechanical and electromechanical properties, and to understand these relationships using mathematical modelling; 2) Employ simulation and experiment to develop and model functional bonding between the dissimilar PDMS and collagen I layers; 3) Optimise the formation of microtissues suitable for cell migration assays; 4) Effectively disseminate knowledge intersectorally between academic and industrial consortium members; and, 5) Perform cell migration assay investigations on 96 well-plate prototypes.

Data: CORDIS, © European Union

Project objective

Cell migration assays are commonly used to study wound healing, cancer cell invasion, and tissue development. Problems associated with the gap closure assays typically employed are that: (i) the stopper or scratch used to make the migration zone damages the extracellular matrix (ECM), (ii) the migration zone size is limited by the size of the stopper, and (iii) the scratched migration zone shapes and sizes are irreproducible. Cell migration is strongly coupled with the structure and mechanical properties of the ECM, and damage to the ECM alters the cell migration path.The main objective of this project is to develop a prototype novel cell migration assay, which will significantly improve the predictive power of cell-based assays while avoiding problems associated with existing assays, based on seeding cells precisely on pristine extracellular matrix tissue mimics with native-like cell-functionality and reproducible migration zones.In accomplishing this, we will also address the following questions:• What are the structure-property relationships between collagen I matrices with controlled thicknesses and fibril diameter and alignment, and their mechanical and electromechanical properties?• What are the critical parameters for achieving functional bonding between the substrate and the highly anisotropic viscoelastic collagen I matrices and controlling the overall mechanical properties?• Does the distribution of collagen fibril polar ordering, i.e., piezoelectric domains, influence cell migration?• What parameters control crimp formation in tendon-like collagen I matrices?• What parameters control and explain the unusual viscoelastic properties (e.g., they not depend on the speed of deformation, at least within the interval 0.01 - 1 mm/sec) of tendon-like collagen matrices?• Which cell types, including cancer cells, co-align with collagen fibril alignment or crimp direction?

Original text from CORDIS.

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Data: CORDIS, © European Union