Computational Fluid Dynamics to infer embryonic tissue rheology
Multi-cellular morphogenesis relies on the ability of tissues to generate internal stresses resulting in large
tissue deformation. At the tissue scale, those stresses can be eﬀectively described through continuum models for tissue deformation, remains poorly understood. Experimentally, the growing ability to engineer in-vitro functional tissues , together with the development of microﬂuidic techniques , open the way to new perturbative approaches to determine tissue mechanical properties. New theoretical and computational approaches are however crucially needed to infer tissue rheology from such experiments. This project aims at developing new inference approaches based on non-Newtonian Computational Fluid Dynamics (CFD) . This will allow us to bridge a crucial gap in the understanding of the mechanics of morphogenesis, and will pave the way to the development of predictive computational models for tissue mechanics.
Tissue morphogenesis; Active matter; Rheology; Computational Fluid Dynamics (CFD)
The PhD project aims to use computations to develop new rheological models for embryonic organoids. (1) We will determine the main ﬁelds (e.g. key protein concentrations) controlling tissue rheology. (2) We will propose simple rheological models recapitulating heterogeneous mechanical properties of embryonic organoids. (3) These models will be applied to the computational modeling of embryonic organoid morphogenesis, in collaboration with a postdoc in the group (ANR-JCJC submitied by Simon Gsell).
Proposed approach (experimental / theoretical / computational)
Sham Tlili (ST) will perform rheological experiments where embryonic organoids are aspired through microﬂuidic channels , while being imaged at the subcellular scale using mul-photon microscopy. The experimental data will consist in heterogeneous velocity and cell deformation ﬁelds, obtained for various tissue types ranging from homogeneous stem cell aggregates to diﬀerentiated organoids. The PhD student will (i) contribute to the experimental data analysis and (ii) develop a CFD program based on the latice-Boltzmann method able to simulate such tissue ﬂows, given some prescribed rheological properties. He/She will perform extensive simulations coupled to a Bayesian inference algorithm  in order to determine the rheological parameters that best predict experimental tissue velocity ﬁelds. By applying our algorithm to various homogeneous tissues, we will determine the impact of tissue biochemical properties on rheology. Our tissue-dependent rheological models will ﬁnally be applied to fully developed heterogenous organoids.
This project is at the interface between developmental biology, biophysics, soft matter physics and
computational physics. It is speciﬁcally designed to address a fundamental question regarding mul-cellular morphogenesis (How can mechanical properties shape tissues ?) and to synergize with emerging experimental techniques (microﬂuidic experiments on embryonic organoids). The project is at the conﬂuence of expertise present at IRPHE (Theoretical ﬂuid dynamics, Computational physics) and IBDM (embryonic tissue culture/engineering, microﬂuidics and 3D imaging) resulting in an original inter-disciplinary program. The use of Computational Fluid Dynamics in the ﬁeld of developmental biology is an emergent trend that may pave the way to the development of new computational tools to better understand and engineer tissue morphogenesis. Heterogeneous mechanical properties emerge in other biological tissues such as tumors and spheroids: for this reason we expect this project to have spin-oﬀ in other ﬁelds such as cancer biophysics.
Applicants should have a background in physics, mechanics or applied mathematics, with some experience in programming and numerical simulations. They should have a strong interest in biological physics/mechanics and be motivated by inter-disciplinary research. Some theoretical knowledge/experience in rheology, active matter, image analysis and/or computational ﬂuid dynamics would also be appreciated.
Is this project the continuation of an existing project or an entirely new one? In the case of an existing project, please explain the links between the two projects
During his CENTURI postdoc from 2020 to 2022, Simon Gsell (SG) developed computational models recapitulating early morphogenetic ﬂows in embryonic organoids, assuming that tissues behave as simple viscous ﬂuids. However, this hypothesis is not valid anymore for more advanced morphogenesis stages, where tissues exhibit complex visco-elasto-plastic mechanical behavior, which is likely to be modulated by cell diﬀerentiation. Both new experimental (ST) and numerical (SG) tools need to be developed to tackle this new question.
2 to 5 references related to the project
-  Jülicher et al., 2018, Reports on Progress in Physics, doi:10.1088/1361-6633/aab6bb
 Simunovic & Brivanlou, 2017, Development, doi:10.1242/dev.143529
 Tlili et al., 2022, Development, doi:10.1242/dev.200774
 Gsell et al., 2021, Journal of Computational Physics, doi:10.1242/dev.143529
 Ran et al., 2023, Journal of Rheology, doi:10.1122/8.0000556
3 main publications from each PI over the last 5 years
(i) Loiseau et al., 2020, Nature Physics, doi:10.1038/s41567-020-0980-z
(ii) Gsell et al., 2020, Scientific Reports, doi:10.1038/s41598-020-64695-w
(iii) Gsell & Merkel, 2022, Soft Matter, doi:10.1039/D1SM01647D
(i) Tlili et al., 2019, PNAS, doi:10.1073/pnas.1900819116
(ii) Tlili et al., 2020, Physical Review Letters, doi:10.1103/PhysRevLett.125.088102
(iii) Hashmi et al., 2022, eLife, doi:10.7554/eLife.59371