William Martinson: Mathematical modeling of leader-follower cell migration in cancer and developmental biology

Vortragender/Speaker: Dr. William Martinson
Ansprechpartner/Contact: Jun. Prof. Dr. Markus Schmidtchen
Videostream (BBB): https://tud.link/1euh

Titel/Title:
Mathematical modeling of leader-follower cell migration in cancer and developmental biology

Zusammenfassung/Abstract:
Collective cell migration is an essential phenomenon in biology, occurring in diverse processes such as neural crest stem cell migration and angiogenesis (the formation of new blood vessels from pre-existing ones). Both phenomena involve cells adopting two phenotypes: a “leader cell” type, which travels towards external biophysical signals, and a “follower cell” type, which responds to leader-created cues. The mechanisms underpinning such leader-follower migration remain poorly characterized in general, in part because they occur over multiple spatial and temporal scales. Mathematical modelling can help resolve such issues, as it can tractably evaluate different biological hypotheses, connect individual cell interactions to collective behavior, and guide the design of in vivo experiments. 

This talk examines open questions relating to leader-follower migration and its mathematical modeling. The first part focuses on theoretical work that determines when different mathematical representations of leader-follower migration will produce similar results, using angiogenesis as a paradigm. By comparing simulations of an existing discrete angiogenesis model to solutions generated from two distinct continuous frameworks, we identify parameter regimes for which all three models yield nearly indistinguishable solutions and uncover implicit physical assumptions that ensure they accurately describe their underlying biology. The second part of the talk focuses on how mathematical modeling can bring new experimental insight into leader-follower migration through the example of chick neural crest cells. We collaborate with developmental biologists to create a novel individual-based model for cranial neural crest cell migration that investigates whether remodeling of an initially naïve and punctate extracellular matrix (ECM) creates a scaffold for trailing cells that enables them to form robust stream patterns. Global sensitivity analysis and simulated gain- and loss-of-function experiments of the model suggest that long-distance migration without jamming states is most likely to occur when leading cells specialize in creating ECM fibers, and trailing cells specialize in responding to environmental cues by upregulating mechanisms such as contact guidance.