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

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Cell migration mapped using nature’s topography

Cells move to where they are needed for wound healing; and they also migrate where they are not welcome as seen in cancer. EU research has investigated the journey cells undergo to find out what drives the process.

Health

Researchers with the MATRIXASSAY project were looking to combine the considerable expertise of their partners and leverage the technological innovations of industrial collaborators to develop a tool to assess cell migration on surfaces.

Much more than scratching the surface

Scratching away a region of cells is a standard method to investigate wound healing and explores how cells close that gap. However, problems can arise when using the so-called scratch assay, as often the underlying surface coating is removed as well. “Of particular importance is that the surfaces reflect the extracellular matrices that cells encounter in the body,” points out Brian Rodriguez, professor of physics at University College Dublin and project coordinator. Undertaken with the support of the Marie Skłodowska-Curie programme, MATRIXASSAY has developed a new method to track the migration of cells. A self-organised cluster of cells, a spheroid or an organoid, is placed directly in the centre of each well of a 96-well tissue culture plate. “To mimic different naturally occurring extracellular matrices within our body, the wells were coated with films of aligned collagen fibrils of controlled diameter,” Rodriguez explains. Other advantages of the MATRIXASSAY is that it’s fully compatible with high content imaging approaches and could be used to investigate the influence of topographic features and mechanical properties. Even the effect of drugs on the ability of the cells to migrate could be tested. Placement of the spheroid reproducibly in the centre of a well can save on time and data storage as there is no need to take multiple images.

Future research progress along nature’s tracks

Rodriguez explains his plans for the direction of research: “Now that we have established the prototype, we hope to use it to explore the mechanical and topographical influence on cell migration for different cell lines, and under different conditions.” Results from the project plus previously published work indicate that depending on the topography of the collagen, some cells will migrate preferentially along the alignment direction, or perpendicular to the alignment. Take tendon structure for example, which is crimped leading to strength as well as shock-absorbing properties.

Diversity brings inherent challenges

“Perhaps any large international and intersectoral project will encounter challenges, despite risk mitigation measures – we certainly had our fair share including difficulties in obtaining visas for the United Sates after the 2016 election!” Rodriguez emphasises. Issues ranged from foreseen technical challenges to the unforeseen departure of a consortium partner. He stresses that researchers tend to underestimate the time and resources needed to deliver on an ambitious workplan. A balance is required between these often-opposing requirements but a healthy imbalance helps to focus efforts and leads to innovation.

Commercial compatibility and multiple applications for biomed part production

“In many ways the work is just beginning, and we hope to refine and publish our work.” MATRIXASSAY design stands on a firm platform. The system is compatible with various commercially-available well plates and well plate inserts. Not limited to the placement of spheroids, the system can also be used to locate microcarriers (cells in a support matrix) in certain locations on 3D-bioprinted constructs for biomedical part fabrication.

Keywords

MATRIXASSAY, scratch, cell migration, extracellular matrices, collagen, well plate, assay

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