H2020Individual fellowship2017–2019

OMICS · Origami-based Microfluidic Interface for Cell Signalling

Horizon 2020 — Marie Skłodowska-Curie Actions

Duration
2017-03-15 → 2019-03-14
EU contribution
€159,461
Participants
1
Scheme
MSCA-IF

Lines connect the coordinator with its partners.

Results in brief

Origami-based Microfluidic Interface for Cell Signalling

Sending and receiving signals is the basis of cell communication. Cell surface receptors react to a multitude of signal molecules and trigger cellular responses that, in turn, regulate organismal homeostasis. The malfunction of receptors and signals in cells may lead to the development of many diseases, including cancer, diabetes, neurodegeneration or autoimmune disorders. Specifically, the epidermal growth factor receptor (EGFR), which is activated after binding of the epidermal growth factor (EGF), is involved in the pathogenesis and progression of various carcinoma types. Moreover, it has been proven that the clustering of this receptor plays an important role in the activation of the cells. Thus, understanding this complex signal pathway is key for future therapeutic approaches and drug development. In addition, a tool capable of bridging this molecular event, that occurs at the nanoscale, with the cellular responses, measurable at the micro and mesoscale, is needed. We aimed to develop a microfluidic platform to mimic closer the natural cell environment for the study of early EGFR-EGF signaling cascade in epithelial breast cancer cells. To this end we applied a technology recently developed that is based on the use of DNA origami nanostructures as molecular pegboards for presenting ligands to cells with a full control of their absolute number, stoichiometry and nanoscale orientation.

Data: CORDIS, © European Union

Project objective

Cell surface receptors react to a multitude of signal molecules that trigger cellular responses and regulate cell fate. The malfunction of receptors and signals in cells may lead to the development of many diseases, including cancer, diabetes, neurodegeneration or autoimmune disorders. Thus, understanding complex signal pathways is key for future therapeutic approaches and drug development. This project concerns the development of a high throughput microfluidic device for the investigation of early cell signalling, which is triggered by ligand-decorated DNA origami nanostructures, immobilized on a microarray-patterned surface inside the microfluidic device. By combining state-of-the-art top-down microstructuring and bottom-up self-assembly, this approach allows to present ligands on surfaces with a full control of their absolute number, stoichiometry and nanoscale orientation, enabling to closer mimic the natural cell environment. While the principal functioning of origami-based ligand presentation has very recently been demonstrated by the beneficiary, the here proposed implementation in a microfluidic chip will improve surface stability and robustness, as well as allow automated, on-surface assembly and cell culture processes to open the door to multiplexing and high throughput analyses.

Original text from CORDIS.

Participants

  • KARLSRUHER INSTITUT FUER TECHNOLOGIE · KarlsruheCoordinatorGermany

Links

Data: CORDIS, © European Union