PhD Discussions Sessions: Ariadna Marin and Ignasi Casanellas

Linking epithelial size, tension and pressure in curved epithelial monolayers

Epithelia are thin cellular layers that act as mechanical and biochemical barriers. They are dynamic tissues that present strong intercellular junctions needed to maintain their integrity while growing and regenerating. During embryogenesis, they fold progressively and give rise to highly reproducible 3D shapes that guide the shape and positioning of organs.

The way pressure and tension depend on the size of 3D epithelial structures can help us understand how epithelia fold into determined shapes and are able to maintain them even under the continuous remodelling due to cell division. In this project we generate simple fluid-filled MDCK 3D monolayers to study the link between epithelial size, luminal pressure and intercellular tension.

Nanoscale surface adhesiveness continually modulates intercellular communication in cartilage development

Nanoscale inputs of the extracellular matrix (ECM) affect cell behavior, including differentiation. We have developed a method for the simple production of large-scale substrates functionalized with cell-adhesive moieties of arginine-glycine-aspartate (RGD) dendrimers, with uneven local densities at the nanoscale.

In the first stages of cartilage formation, mesenchymal stem cells gather together, forming condensates with an extensive gap junctional intercellular communication (GJIC) network. The establishment of this communication network is imperative for the development of healthy cartilage tissue. We have used nanopatterned substrates to locally control cell-substrate adherence during mesenchymal condensation, a prevalent morphogenetic transition, and promote stem cell differentiation towards chondrogenesis. We here demonstrate that local ligand density defines gap junctional protein Cx43 network architecture and GJ functionality.

By a condensate transplantation assay, we then reveal that differentiating stem cells are sensitive to evolving substrate inputs in a continuous feedback mode after condensation. The renewal of optimal ligand conditions led to a revamp of Cx43 expression.

This knowledge provides new insight into cell-matrix nanoscale interactions during morphogenesis. It is relevant for the design of nanopatterned platforms for cell-based regenerative therapies of mesenchymal tissues such as cartilage.

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