A Theoretical Exploration of the Growth and Stability of Alveolospheres

Abstract

An alveolosphere is a type of stem cell derived lung organoid. They have a distinct “balloon-like” structure which resembles the alveoli in human lungs. In recent years, they have become increasingly popular as model systems for disease research and treatment development, especially with the onset of COVID-19. Patients born with a rare mutation on both copies of their SFTPB genes face severe respiratory issues after birth which often lead to poor outcomes. Lung cells derived from the stem cells of patients with this double-mutation fail to form the complex structure indicative of successful alveolosphere development. The tension-dominated nature of this structure reveals that the biology of the formation of alveolospheres is heavily coupled with their mechanics. Therefore, in order to fully understand an alveolosphere’s biology it is essential to understand its mechanics. This thesis outlines a theoretical framework which, in conjunction with targeted experiments, could serve as the basis for a mathematical theory of the development and growth of alveolospheres. Such a theory would provide a better understanding of what needs to go right, and what can go wrong, during alveolosphere development. By extension, this framework offers a path forward towards the discovery of new treatments for genetic and pathological lung diseases that directly affect alveoli.