Shaping intestine epithelium using viscoelastically dynamic matrices

Intestine epithelium (IE) compartmentalization and morphogenesis are profoundly influenced by intrinsic biochemical signals and microenvironmental cues in the extracellular matrix (ECM), especially viscoelasticity.

Recent studies have revealed substrate mechanical properties have clear influences on intestine stem cell (ISC) fate, IE polarity, self-organization and morphogenesis.

However, most of these investigations were performed in constant and static conditions, neglecting the active and dynamic nature of in vivo ECM.

Furthermore, whether and how dynamic matrix viscoelasticity contributes to the emergence of symmetry breaking and tissue regionalization in early intestinal morphogenesis remains elusive so far.

In this project, we propose to use dynamic hydrogel-based matrices with light-triggerable changes in viscoelasticity to study the transduction of molecular mechanosensing into collective cell dynamics during symmetry breaking and tissue patterning in IE development.

We hypothesize that anisotropic substrate viscoelasticity could heterogeneously activate mechanosensing pathways in ISCs and affect ISC proliferation and differentiation, leading to changes in cell activities, sorting and tissue segregation.

In brief, with dynamic substrates, we will create viscoelastic patterns/gradients by in situ light patterning and elucidate IE dynamics related to the emergence of cell shape, migration, ISC fate and tissue compartmentalization as functions of the mechanical stimuli.

We also aim to identify the molecular principles of IE mechanotransduction, which will improve our understanding of IE development, morphogenesis and homeostasis.

The know-how from this project will also enable the fabrication of artificial intestine-on-a-chip devices for further developmental studies.

Relying on the multidiscipline approaches, this action will greatly enhance the competence of the researcher as well as bring added value in scientific and societal aspects for the EU.