Microfluidic flow of vesicle prototissues – LOVETISS

The goal of the LOVETISS project is to provide a comprehensive description of tissue rheology, linking the physics at the cell and tissue scales, based on a novel biomimetic approach. We will characterize the flow of biomimetic vesicle prototissues, as a simplified model for cellular tissue flows observed in complex physiological problems.

The rheology of biological tissues is in intimate relation to the mechanical properties of individual cells. During embryogenesis cells collectively migrate, leading to the formation of different tissue layers. In this dynamical process cell-cell adhesion and cortex contractility have antagonistic effects, the first enhancing cell-cell spreading and the later favouring cell surface minimization (but both mechanisms being interdependent). Likewise, adhesive properties of cells also dictate the flowing behaviour of tumours in metastasis, greatly influencing its potential invasive capabilities. The ability to systematically change physical cell properties in animal models is limited (as it exists interdependence between different components) and it becomes extremely challenging to design experiments which enable to dissociate and understand the role of each of them. The LOVETISS project aims at characterizing the flow of vesicle prototissues, as a simplified model for cellular tissue flows. Giant unilamelar vesicles (GUVs) constitute an excellent biomimetic cell model of intermediate complexity, as they reproduce key essential mechanical features of living cells but disregard complex signalling networks. Vesicle prototissues are obtained by the controlled assembly of GUVs. Thanks to the unique possibility of vesicle prototissues to tune their physical properties independently, we will be able to isolate and decipher their individual role on the rheology of the overall tissue.

To this purpose, we will first optimize the assembly of vesicle prototissues in order to enhance its biomimetic potential. By taking advantage of the DNA-technology, we will implement programmable GUV-GUV adhesion, to tune their adhesion strength and facilitate dynamic vesicle assembly. Complementarily, we will control the elastic properties of individual vesicles, and will encapsulate an active gel inside them, with the goal of mimicking the essential mechanical ingredients of cell membrane and cytoskeleton.

The flow behavior of vesicle prototissues will be investigated in microfluidic confinement. Aspiration experiments are intended to quantify its material properties (elastic modulus, shear viscosity and relaxation time). For this, we will implement the necessary image analysis tools in order to provide a comprehensive description of the flow at the global scale (deformation and velocity of the overall tissue) and at the local scale (GUV deformation, rearrangements and velocity field). Both the role of GUV adhesion and elasticity will be assessed. We will be able to selectively evaluate the impact of adhesion on the occurrence of GUV rearrangements under flow, which takes place in competition with GUVs deformation. And using active vesicle prototissues we will be able to answer to the question, whether the flow of active biomimetic tissues can be self-propelled.

Finally, we will establish the theoretical constitutive equation (viscoelastic or visco-elasto-plastic) capable of reproducing the rheological behavior of the prototissues. Comparison will be addressed between microfluidic flow experiments of biomimetic prototissues and of tissue explants from Xenopus embryos, which will make possible to uncouple the role of physical mechanisms from intricate mechano-sensing or molecular processes present in living tissues. Overall, we believe the scientific findings of LOVETISS will significantly contribute to the understanding of tissue rheology, sheding light on the role of physical cues taking place in morphogenesis and tumour metastasis.