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Anwar Md Nurul
Nice talk Jess
Very cool work! Maybe I missed it: Does the basement membrane (or will it in a future model) be degraded/built up in new places? How does that (or would that) work?
Id like to ditto Erikas question! Was just wondering that too :)
Beautiful work Daria! I missed how new cells appear in the network, if you account for cell division or if they come from the base of the sprout. I ask because I was involved with the Japanese team that made the movies of cell mixing you showed. In those experiments most new cells in the network came from the base of the sprout.
Thanks, Alvaro! So right now, cells are supplied at the boundary at the point of the sprout initiation. We saw that the prolifiration rate was very small at the timescale of initial sprout formation and we didn’t take it into account in the model. So this boundary condition mimics a constant cell supply from the underlying vascular bed. Now we’re extending our work to larger scale simulations and we are implementing cell proliferation.
It would be very interesting to try to compute this ‘mixing measure’ for the data from the japanese experimentalists if you have access to the data!!
I’ll try to get them and mail you and Tomás.
Fascinating work Katie. Thank you so much for the presentation. Filopodia sense the environment for biochemical and mechanical signals (as in astrocytes on retina vascularisation). I was wondering how the microenvironment can influence the timing of notch inhibition. I.e. depending on what filopodia meet as they grow and sense their neighbourhood...
thanks Rui! - that’s is a great question!! I would love to know how different things they encounter impact the feedback to sensing and downstream timing effects
We are setting up some micro patterning in vitro experiments now to start micro manipulating the filopodia and their microenvironment to see if we can detect timing changes in the cell-cell patterning
I was wondering about that as well, is the basement membrane formed at this stage of development? The filopodia don’t have to worry about that do they?
wow! looking really forward to see the results. exciting stuff. congratulations!
So yes, my understanding if the BM is slower to be deposited so shouldn’t impact fils early on but good idea, as the timing of that depositing over time could impact fils extended from newly deciding cells in regions further back
Very interesting, thanks Kate
@Jess At this early stage the basement membrane is still immature I think. There has been some work showing that hyaluronidase is needed for sprouting to start.
Daria, nice model! - I’m wondering if you might implement time-delayed Notch ODEs, to see if you can recapitulate the notch oscillations in high vegf in your model? (As per Ubezio et al 2016) :)
Thanks Katie! Yes, the subcellular model can be changed. Since there are many models of Delta-Notch signalling, we just chose one that looked not very complex so that we don’t increase the computational complexity of the model. But yes, definitely, I can put the other model inside and see what results it produces. Great idea!
Hi Daria. I liked you work a lot. I was wondering have you also simulated mixtures of WT and VEGFR2+/- like in the Jakobsson 2010 paper?
Hi Lowell, great work! regarding intercalation. is there also an attractive force between ECs beyond adhesion and I missed if there is something like a BM around the vessls?
Id be happy to chat more about it and other cell rearrangement features if you’re interested Daria, as its a nice multiscale setup that seems quite modular for extensions :)
Thank you, Roeland! Yes, we actually did it for model validation and we compared their results regarding which cell ends up at the leading position of a sprout. We haven’t included any simulations of a full network growth formed by mixture of cells (WT:mutant). But we definitely should later!
Nice! What was the result?
Great, Katie! I’ll drop you an email then!
@Roeland the model reproduced very well the competition between mutant and WT cells for the leader position