SOCELL · Self-organized biomolecular gradients for controlling cellular behaviour in cell culture
Horizon 2020 — Marie Skłodowska-Curie Actions
- Duration
- 2018-08-01 → 2020-07-31
- EU contribution
- €173,076
- Participants
- 1
- Scheme
- MSCA-IF-EF-ST
Lines connect the coordinator with its partners.
Results in brief
Self-organized biomolecular gradients for controlling cellular behaviour in cell culture
Programmed into their genetic code, cells are capable of knowing when and into what cell type they must differentiate into. While some factors are purely genetically programmed (senescence expression of genes), others are triggered by extracellular cues, such as by small biomolecules or forces. In particular, specific combination and concentration of biomolecules have shown to be very important during morphogenesis. As an example, the embryo of the fruit fly is capable to differentiate the anterior from the posterior region due to the gradient of a specific molecule released by the mother. Other more complex gradients of biomolecules have been described as the reason for other patterns observed in nature. For this reason, the scientific community has made efforts during the last century in developing methodologies to recreate biomolecular gradients. The achievement of these biomolecular gradients would not only help to better understand complex steps during embryogenesis, but would aid in developing better bioengineering tools and smart bandages. In this project we have decided to approach the development of biomolecular gradients from a new perspective. While conventional methods rely on a passive mechanism (gradients disappear with time if not actively re-formed), we decided to develop active mediums, where there are capable of forming and keeping their own gradients (self-organized). Due to its programmability and robustness, we have decided in using DNA Nanotechnology as the machinery capable of forming and keeping the gradients. In order to do this, we have divided the project into 3 main objectives: 1. Functional DNA programs in the presence of living cells (due to their biocompability). 2. The DNA machinery has to alter the cellular behaviour. 3. The DNA machinery must have spatiotemporal control over the cellular fate. We had foreseen this project to be laborious from the beginning, but we were capable of developing an active extracellular medium which had spatiotemporal control over living cells with the use of DNA programs. Being the first example of an out of equilibrium DNA program capable of working in the presence of living cells, we foresee it will be largely welcomed by the scientific community, due to its large possibilities and applications.
Data: CORDIS, © European Union
Project objective
Concentration gradients of biomolecules are essential in important biological events such as morphogenesis, inflammation, wound healing and cancer. As a consequence, devising methods to generate highly controlled biomolecular gradients for studying cellular behaviour is a major scientific endeavor. However, state-of-the-art approaches based on microfluidics suppress cellular signalling by washing molecules away, limiting their biological significance. To solve this issue, this proposal will develop an original method to create biomolecular gradients that influence cellular behaviour without interfering with cellular communication. This method relies on recent DNA nanotechnology developments in the host group that create complex ssDNA concentration gradients autonomously, through a reaction-diffusion mechanism. The goal of this proposal is to demonstrate that such self-organized concentration patterns of DNA strands can modify the gene expression of human cells in vitro. Antisense technology will be used to couple extracellular DNA gradients with changes in cellular behaviour. As a proof of principle, a two-band concentration pattern of DNA will be created, which will induce in vitro a similar pattern of fluorescent protein expression on a HeLa cell monolayer. As an application, biomolecular gradients will be used to control wound healing assays, allowing the patterning of cell culture. These results would open doors to control and study cellular behaviour while maintaining crucial cellular communication mechanisms. In the long run, this technique, that combines the self-organization of synthetic molecules and living cells, could be advantageously used in tissue engineering.
Original text from CORDIS.
Participants
- SORBONNE UNIVERSITE · ParisCoordinatorFrance
Links
Data: CORDIS, © European Union