Tissue units constructed by extracellular matrix mimics based on bioengineered silk

The availability of relevant in vitro models of tissue units would be highly valuable for our struggles to understand human biology and physiology to obtain better health solutions.

In the native tissue, cells are organized by a supporting extracellular matrix (ECM) in various types of microenvironments.

ECM proteins build up the frameworks of these different environments, e.g. interstitial fiber networks in connective tissue and basement membranes in biological barriers.

It has lately become clear that cells in culture are largely affected by their microenvironment, and especially mechanotransduction and the availability of cell-cell and cell-matrix connections.

We will herein use a functionalised recombinant spider silk protein to construct relevant ECM-mimics, both networks for parenchymal and support cells in tissue compartments, and membranes for their biological barriers. These we will use to survey the effect of different parameters of the environment for cells in culture.

For investigations of biological processes, it is essential to include a combination of cellular compartments and biological barriers.

We will use our obtained knowledge to construct physiologically relevant tissue units of 1) tumours in stroma with blood vessels, for investigations of the interplay between cancer cells and vasculature, as well as 2) tumours behind blood brain barrier (BBB), for investigation of treatment strategies of brain tumours.