Bridging scales: how mechanotransduction detects topological defects for morphogenesis

• Applicant: Dr. Julia Eckert
• Subject Area: Statistical Physics, Nonlinear Dynamics, Complex Systems, Soft and Fluid Matter, Biological Physics ; Biophysics ; Cell Biology
• Term: since 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 553948485

This project seeks to understand how tissue geometry directs epithelial morphogenesis. I aim to address the broad question of how individual cells ‘know’ how to collectively arrange to generate complex three-dimensional structures. It has recently been proposed that topological defects, specific perturbations in the collective alignment of cells, drive morphogenetic events, possibly by generating regions of high mechanical stress within tissues. For this to occur, there must be molecular mechanisms that respond to tissue-level stresses to elicit cellular responses, such as cellular rearrangement and motility. But what those mechanisms are is unknown. Here, an important challenge is to understand how to bridge across biological length and time scales, from molecular mechanisms (nanometer/micrometer, seconds) to multicellular rearrangement (millimeter, minutes/hours). I hypothesize that mechanical stress generated by topological defects is detected by mechanotransduction mechanisms at cell-cell adherent junctions to engage morphogenetic responses. This means that the cells sense changes in tissue stress and convert these stimuli into biochemical signals to respond to the extracellular cues. Using my expertise in cell and tissue mechanics, soft condensed matter physics, and especially in the characterization of two-dimensional tissue geometries and image analysis, I will test this hypothesis by investigating how epithelial aggregates break symmetry to generate multicellular protrusions. Specifically, I aim to identify spatiotemporal relationships between junctional RhoA signaling and topological defects by combining live-cell imaging of biosensors, novel developed tools for quantitative image analysis, and concepts from active condensed matter theory. To establish whether these correlations reflect causal relationships, I will test their stability by perturbing mechanotransduction mechanisms at adherent junctions using cutting-edge cell-biological tools. If successful, this will identify cellular mechanisms that allow tissue geometry to drive morphogenesis, providing key insight into how these complex biological phenomena arise as emergent properties that bridge between the molecular and supra-cellular scales.

• DFG Programme: WBP Fellowship
• International Connection: Australia
• Host: Professor Alpha S. Yap, Ph.D.