Mechanotransduction in organoid development

Mechanotransduction in organoid development #

Kieran Boniface

14:10 Monday in 3Q68.

Part of the Cell and tissue mechanics session.

Abstract #

Organoids, mini engineered tissues, have become increasingly popular in recent years [1]. Indeed, we are experiencing an explosion of interest in organoids as three-dimensional test beds for biological experiments due to their complex structure and ability to mimic in-vivo tissues [2]. As a result, work must be done to accurately grow and develop organoids. However, the development of organoids, like all biological tissues, is sensitive to the mechanical signals that can influence behaviour from cell growth to determining cell type and shape [3]. These mechanical cues can even override biochemical signalling in directing type specification of stem cells [4]. This is made more complex in multicellular structures where mechanical signals operate over multiple length scales. Thus, mathematical models can provide an elegant framework to shed light on the underlying mechanics. One class of models are those founded in a consideration of continuum elasticity [5] as applied to soft tissue mechanics, providing the opportunity to investigate the role of key mechanical factors [6]. The challenge is to produce models that can capture the active behaviour of cells and their ability to generate force as well as to describe the passive mechanical interactions of the system. We present here a model that captures key force generating mechanisms of organoids, namely cell contractility and cell growth. We describe the interaction between contractility and tissue growth and how their antagonistic behaviour can introduce key mechanical signals that may influence behaviour. As a final step, we consider the potential mechanisms by which mechanical feedback into cell control can be incorporated into our model and the impact this will have.

References

  1. Schutgens, F. & Clevers, H. Human Organoids: Tools for Understanding Biology and Treating Diseases. https://doi.org/10.1146/annurev-pathmechdis-012419-032611 15, 211–234 (2020).
  2. Kim, J., Koo, B. K. & Knoblich, J. A. Human organoids: model systems for human biology and medicine. Nature Reviews Molecular Cell Biology vol. 21 571–584 Preprint at https://doi.org/10.1038/s41580-020-0259-3 (2020).
  3. Orr, A. W., Helmke, B. P., Blackman, B. R. & Schwartz, M. A. Mechanisms of Mechanotransduction. Dev Cell 10, 11–20 (2006).
  4. Engler, A. J., Sen, S., Sweeney, H. L. & Discher, D. E. Matrix Elasticity Directs Stem Cell Lineage Specification. Cell 126, 677–689 (2006).
  5. Taber, L. Alan. Nonlinear theory of elasticity applications in biomechanics. Nonlinear theory of elasticity applications in biomechanics (World Scientific).
  6. Littlejohns, E. & Dunlop, C. M. Mechanotransduction mechanisms in growing spherically structured tissues. New J Phys 20, 043041 (2018).