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Multiscale Modelling of Microfluidic Cell Mechanoporation for Intracellular Gene Delivery

Project description

3D multiscale model to advance gene delivery

Intracellular gene delivery is crucial for mRNA vaccines, CAR-T cell therapy, and plant genetic engineering. Microfluidic delivery is a simpler alternative to traditional methods but often relies on trial and error due to limited predictive tools. Supported by the Marie Skłodowska-Curie Actions programme, the M2-CPID project will develop a 3D multiscale model to predict cell deformation, membrane mechanoporation, and the delivery of genetic material in microfluidics. It will conduct experiments to measure cell membrane pores and gene concentrations, using the data to validate the model. The project will also explore how flow conditions, cell mechanical properties, and the molecular weight of genetic materials affect cell membrane poration, cell viability, and gene delivery efficiency.

Objective

Intracellular gene delivery has ground-breaking applications in mRNA vaccines, preparation of CAR-T cells for cancer treatment, and genetic engineering of plants. Microfluidic-based delivery, which uses fluid flow to disrupt cell membranes, leading to transient formation of membrane pores and internalisation of genetic materials, is emerging as a simple, universal, and transformative approach compared with classical methods that utilise electroporation or viral vectors. However, development of microfluidic-based approaches has been conducted largely through trial-and-error experiments, due to the lack of a high-fidelity predictive simulation tool.

This interdisciplinary fellowship will integrate the fellow’s strong expertise in modelling fluid-structure interaction and nanoscale membrane damage, with the host’s experimental expertise in cell mechanics and microfluidic intracellular delivery. It will develop an accurate predictive simulation tool and fundamental understanding of microfluidic flow-induced cell poration, and the associated internalisation of exogenous genetic materials. Specific scientific aims are: 1, to develop a novel three-dimensional multiscale model, to enable quantitative predictions of cell deformation, membrane mechanoporation and intracellular delivery of genetic materials in microfluidics; 2, to conduct systematic experiments, measuring cell membrane pores and gene concentration inside cells, and use the data to validate the model; 3, to combine simulations and experiments to uncover the effects of flow condition, cell mechanical property and molecular weight of genetic materials, on cell membrane poration, cell viability and gene-delivery efficiency.

Through carefully planned knowledge transfer, dissemination and trainings, the fellowship will significantly enhance the fellow’s career perspective for establishing independence, and contribute to the EU Research and Innovation Strategy in improving and protecting people's health.

Keywords

Programme(s)

Topic(s)

Funding Scheme

HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships

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Call for proposal

(opens in new window) HORIZON-MSCA-2025-PF

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Coordinator

QUEEN MARY UNIVERSITY OF LONDON
Net EU contribution
€ 276 187,92
Address
327 MILE END ROAD
E1 4NS LONDON
United Kingdom
Activity type
Higher or Secondary Education Establishments
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Total cost
No data