Understanding Mesenchymal Tissue Mechanics via Nanorobotics (360G-Wellcome-302541_Z_23_Z)

Cells interpret and modify tissue mechanics to regulate behaviours such as migration and differentiation in development and disease. A prominent example is the epithelial-mesenchymal transition (EMT) that controls the formation of normal mesenchymal tissues as well as metastasis. During EMT, cells remodel the extracellular matrix, potentially in response to and creating changes in tissue forces and rheology. This interplay remains poorly understood due to the lack of tools suited for the fluid-like, heterogeneous and dynamic mesenchymal tissue structure. Recent advances in functionalized micro/nanoparticles provide versatile, bio-compatible sensors at cell and tissue scales. Here I propose to establish nanorobotics as a mechanical sensor and actuator in the paraxial mesoderm of avian embryos, a model mesenchymal tissue. We will 1) develop experimental and theoretical frameworks of interpreting nanoparticle dynamics in the extracellular space; 2) measure the spatiotemporal dynamics of tissue rheology across the paraxial mesoderm, including its formation and differentiation; 3) perform local modulation of tissue mechanics using nanoparticle swarms and record cell and molecular responses using -omics and imaging approaches. The tools established in this project will not only enable an integrated understanding of mesenchymal tissue mechanics, but also lay foundations for "magnetic nanomedicine" including targeted drug delivery and EMT control.