An implantable sensor network for large-scale cellular force mapping in living embryos

Abstract

Mechanical forces generated by cells are fundamental regulators of embryonic development, yet how locally generated forces are integrated across tissues to drive large-scale morphogenesis remains poorly understood. Addressing this question requires direct quantitative mapping of intercellular forces across tissue scale with cellular resolution while preserving native tissue architectures and dynamics, a capability not yet achieved. Here, we introduce FORCENET, an implantable force-sensing network that enables quantitative tissue-scale force mapping at cellular resolution within living embryos. FORCENET consists of a microfabricated network of ultrathin elastic sensors whose three-dimensional deformations are tracked over time and converted into intercellular force maps through physics-based reconstruction. FORCENET covers hundreds of cells while occupying a total volume 6- to 20-fold smaller than that of a single cell. Anatomical measurements, three-dimensional fluorescent imaging, and cell density and speed tracking confirmed that FORCENET seamlessly integrates within developing embryos without perturbing cell motion and proliferation, tissue architecture, and embryonic development. Applied to zebrafish gastrulation, FORCENET revealed that intercellular forces are dynamically coordinated across supracellular length scales of ~30-210 m. Inhibition of fibroblast growth factor signaling accelerated force accumulation and shortened the force-coordination length scales despite only modest changes in cell density and kinematics, demonstrating that FORCENET uncovers information not readily inferred from cell tracking alone. FORCENET establishes a scalable platform for in vivo force mapping and reveals that cell-generated forces are coordinated into supracellular mechanical patterns that are regulated by developmental signaling.