For a single fertilized egg cell to form into an embryo, there are many intermediate steps, including repeated cell division and development of organs in the correct location. But the details of this process and its regulation have yet to emerge. For example, in the sea squirt -- a simpler system than the human embryo but one that shares a lot of commonalities -- a pair of cells is the starting point of the heart of this organism. These cells must move from their origin to the future location of the heart guided by cues from inside the embryo. As the paired cells move, they must push other cells out of their path to reach their destination, all while not losing contact with each other. Although observational studies of the coordinated movement of groups of cells involved in organ formation advance knowledge of embryonic development and associated congenital conditions, this project will deepen understanding by employing mathematical modeling and computer simulations to tease out the many facets of this process. The project will involve developing new computer simulation schemes for the mechanical interactions between cell boundary and interior dynamics, new models for the biochemistry needed to initiate collective migration, new methods for efficiently solving equations in deforming, moving geometries, and extensions to full three-dimensional domains. The investigators will use the interdisciplinary nature of the project to recruit and train undergraduate and graduate students.
The study of collective locomotion of organisms has led to important mathematical models that have guided biological discovery. A distinguishing feature of this project is that the multi-body interaction is achieved through mechanochemical bonds that interact with the cell's biochemistry and biomechanics in an unknown way. We focus on the collective migration of two cells in the early stages of heart development of the sea squirt Ciona intestinalis, an important model organism. Initially, these two cells are indistinguishable, yet at some point they establish leader and follower roles and move with distinct morphologies, squeezing through deformable tissues. Experiments show there is an advantage to move as a cohesive pair rather than a single cell, however, it is unclear why two cells do not slow each other down. These observations lead to the following questions: How are intracellular mechanics integrated to give rise to motility as a cohesive group? Why can two cells move faster together than alone? Is the two-cell system better at polarization and initiating migration than an individual cell? Mathematical modeling can aid experiments in answering these questions, but numerical solutions of the model equations will require development of novel computational methods that will be able to simulate coupled mechanical, transport, and chemical reaction equations in complex evolving geometries. Collaboration with an experimental lab will result in the discovery of a set of minimal yet sufficient interactions underlying the mechanical and biochemical organization of a cohesive cell group.
This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.
