Microfluidic platform for biomimetic tissue design and multiscale rheological characterization

TL;DR

This paper introduces a microfluidic platform for creating and analyzing biomimetic tissues, enabling multiscale rheological characterization from individual cell-like vesicles to tissue-level behavior, advancing understanding of tissue mechanics.

Contribution

The work develops a microfluidic device for assembling and characterizing biomimetic tissues with tunable properties, providing a multiscale rheological analysis framework.

Findings

Flow behavior varies from viscous to viscoelastic with adhesion levels.

Local GUV reorganizations dominate viscous flow at low adhesion.

Internal reorganizations and GUV deformation contribute to viscoelasticity at high adhesion.

Abstract

The way living tissues respond to external mechanical forces is crucial in physiological processes like embryogenesis, homeostasis or tumor growth. Providing a complete description across length scales which relates the properties of individual cells to the rheological behavior of complex 3D-tissues remains an open challenge. The development of simplified biomimetic tissues capable of reproducing essential mechanical features of living tissues can help achieving this major goal. We report in this work the development of a microfluidic device that enables to achieve the sequential assembly of biomimetic prototissues and their rheological characterization. We synthesize prototissues by the controlled assembly of Giant Unilamellar Vesicles (GUVs) for which we can tailor their sizes and shapes as well as their level of GUV-GUV adhesion. We address a rheological description at multiple scales which comprises an analysis at the local scale of individual GUVs and at the global scale of the prototissue. The flow behavior of prototissues ranges from purely viscous to viscoelastic for increasing levels of adhesion. At low adhesion the flow response is dominated by viscous dissipation, which is mediated by GUV spatial reorganizations at the local scale, whereas at high adhesion the flow is viscoelastic, which results from a combination of internal reorganizations and deformation of individual GUVs. Such multiscale characterization of model biomimetic tissues provides a robust framework to rationalize the role of cell adhesion in the flow dynamics of living tissues.