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Alexander George

Publications and source records attributed to Alexander George.

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Cell Migration Boundary Motion in Drosophila Egg Chambers: A Combined Phase Field and Chemoattractant Model

In the Drosophila melanogaster egg chamber, the collective migration of border cells toward the oocyte is guided by spatial gradients of chemoattractants. While cellular responses to these cues are well characterized, the spatial distribution of chemoattractant within the tissue remains difficult to measure experimentally due to imaging limitations and extracellular complexity. In this study, we develop a spatially resolved mathematical framework to model local chemoattractant concentrations during border cell migration. We use a phase-field approach to represent the egg chamber geometry and define a diffusion-reaction system with spatially heterogeneous diffusivity that accounts for confinement by cellular domains. This framework allows chemoattractant diffusion to be restricted to extracellular space while remaining excluded from the interiors of nurse cells, the border cell cluster, and the oocyte, similar to what we observe in vivo. We simulate secretion from the oocyte and degradation throughout the domain, showing how geometry shapes the distribution of signaling molecules. We further couple this chemical field to a mechanical model of cluster migration that includes a tangential interface migration (TIM) force, allowing the cluster to respond to both chemoattractant gradients and cell-cell contact. Our results show that signal localization and tissue geometry jointly influence directional persistence and the speed of migration. Notably, geometric bottlenecks and intersections can flatten local gradients and slow migration, consistent with experimental observations. This modeling framework offers a tool to investigate how biophysical constraints shape signaling environments and guide collective cell movement in vivo.

math.AP

Phase-Field Modeling of Border Cell Cluster Migration in Drosophila

Collective cell migration is a fundamental biological process that drives events such as embryonic development, wound healing, and cancer metastasis. In this study, we develop a biophysically informed phase-field model to investigate the collective migration of the border cell cluster in the Drosophila melanogaster egg chamber. Our model captures key aspects of the egg chamber architecture, including the oocyte, nurse cells, and surrounding epithelium, and incorporates both mechanical forces and biochemical cues that guide cell migration. We introduce the Tangential Interface Migration (TIM) force which captures contact-mediated propulsion generated along interfaces between the border cell cluster and surrounding nurse cells. Our simulations reveal three key features of TIM-driven migration that distinguish it from previous forms of chemotaxis: (1) the necessity of border cell-nurse cell overlap to initiate movement (i.e., border cells cannot move without a nurse cell substrate), (2) motion is tangential to border cell-nurse cell interfaces, and (3) persistent migration even in regions where the spatial slope of chemoattractant is decreasing. Additionally, we demonstrate that with or without geometry-mediated alterations in chemoattractant distribution such as at intercellular junctions we can vary induced migration pauses, independent of mechanical confinement. We capture an experimentally observed transition to dorsal migration at the oocyte with a sustained medio-lateral chemical cue of small amplitude. The results show how spatial constraints and interfacial forces shape collective cell movement and highlight the utility of phase-field models in capturing the interplay between tissue geometry, contact forces, and chemical signaling.

q-bio.CB