How does a cell in an organ know what overall size the organ has? How does the cell decide when to stop dividing once the organ has reached the right size? Which clues cells take from their micro-environment, and how they process them to make decisions, are important open questions.
Understanding such feedback loops between cell growth and mechanics as well as chemistry could have important impact not only in developmental biology (where morphogensis, i.e. how form is obtained, is of interest) but also in medicine: Understanding the growth-chemo-mechanical feedback loops would allow to understand why some tissues grow in a healthy (physiological) way, and why others grow in uncontrolled fashion, such as tumors and cancer. Present models have a lot of difficulties describing how size is determined via growth-chemomechanical feedback.
The seemingly simple and natural requirements that 1) mechanical stress is modeled, 2) growth has a limit and 3) the model is shown to be consistent with the second law of thermodynamics are almost never met by one single model, and require large and complex models with many parameters to be even approximately achieved. This project proposes a paradigm shift in which intrinsic curvature (the scalar curvature of the metric tensor of growth) in a growth process is regulated. This relatively simple hypothesis shows promising results in fulfilling all three requirements listed above. Furthermore, the concept of intrinsic curvature as a regulator of growth at multiple scales will be explored both at the cell level and at the tissue level. Finally, the spatial distribution of intrinsic curvature in growing living tissues will be experimentally tested.
The present project aims at addressing these questions through theoretical modeling that will be developed in collaboration with Giuseppe Zurlo, at the mathematics department of National University of Ireland (NUI) Galway. Further, a collaboration with Eoin McEvoy, a bioengineer at NUI Galway, will enable to experimentally determine the spatial distribution of intrinsic curvature in a tumor spheroid.
This project involves a collaboration between the laboratory LIPhy and the National University of Ireland in Galway (School of Mathematical & Statistical Sciences and Engineering department)
School of Mathematical & Statistical Sciences and Engineering Department, University of Ireland (Galway)