Physicochemical signals define the form, form dictates function.
Overall, the research on tissue morphogenesis and especially the role of physical cues in the formation of the tissue shapes and functionality is leading to new and innovative approaches in tissue engineering and microphysiological system (MPS) models. This research has the potential to revolutionize the way we understand how cells build and shape their environment at different scales, using environmental stimuli as building blocks. It will also help understanding some diseases linked to a loss in the morphofunctionality of individuals or groups of cells and could help create new tissues and organs that are complementary solutions to animal testing and conventional in vitro experiments for mechanistic studies, drug testing, cell therapy and transplantation.
Physical messages influence as much as soluble messages.
Tissue morphogenesis is the process by which cells and tissues self-organize into complex three-dimensional structures. It is a fundamental process in biology, and it is essential for the development of all multicellular organisms. Extensive recent scientific research has revealed a number of new insights into the role of physical cues in tissue morphogenesis. For example, it was shown that mechanical forces from neighboring cells and the extracellular matrix can regulate cell differentiation, gene expression, cell adhesion, migration and proliferation and cell death. Sometimes, mechanical messages hamper or limit the influence of molecular ones, even. The field of mechanotransduction has shed new light on how cells integrate these stimuli as part of their instructions to function. This is why many people now study the role of some important cues such as flow shear stress, ECM mechanics and bioelectricity. Many very interesting and impacting research articles are published these days, that show the collaborative or sometimes initial influence of mechanics in morphogenetic processes.
Our take on morphogenesis.
Inspired by the works and ideas of D'Arcy Wentworth Thompson, Conrad Waddington, René Thom, Lakshminarayanan Mahadevan and others, we are looking at how forms are scuplted in Nature. We are observing how boundaries and separations (at the core of the definition of a shape as a contrast with its exterior) are made and conserved in tissues, by cells that need to change and separate regions, in order to form distinctive physical frontiers. As others, we are inspired by similarities in other physical domains, where impelling and impeding forces compete and finally come to terms towards a common frontier where shapes are formed. We believe that by recreating special conditions observed in vivo suring development, at the right moments in the right position, it should be possible to instruct cells to enter specific programs and show us how they build their environment. We hope cells can teach us what we are fighting so desperately to understand in order to replicate it, as reliably as possible, inside simple tissue models that could help us restore, treat or replace in the future. We will go step by step, using physics, developmental biology and engineering to bring new knowledge in this wide and complex field.
Current work.
We are currently focusing on the vessel morphogenesis, as a fundamental morphological process involving adhesion, migration, proliferation and polarization steps to perform complex 0D (cell) to 1D (line) to 2D (cord) to 3D (tube) transformations with "relatively little" cellular, spatial, temporal and molecular components involved, compared to other more complex architectures.