CAREER: Three-dimensional large-scale biomechanical sensing within developing vertebrates

How living tissues take shape during development is a fundamental question in biology. Genes and biochemical signals are important, but so are physical forces and tissue mechanics. The tools available to measure forces and mechanics are limited. This project will develop new three-dimensional sensing technologies that can be used to map biomechanical properties. Sensor data will be combined with microscopy measurements and computations to map cellular mechanical interactions. The project will use zebrafish embryos as a model system because they develop rapidly, are transparent, and are relevant to vertebrate biology. The results will give new insights into how mechanical, genetic, and biochemical cues guide development. They will also inform tissue engineering and regenerative medicine strategies. Students will participate in the research, which will help encourage interest in science and engineering careers. Mechanical cues, together with genetic and biochemical signaling, regulate key biological processes such as development, homeostasis, wound healing, and tissue regeneration, while aberrant mechanics contribute to disease. Despite its importance, progress in biomechanics has lagged genetics and biochemistry due to limited tools to measure and manipulate forces in living three-dimensional tissues. This project will address this gap by integrating bioelectronics, advanced microscopy, and computational approaches to enable multiscale mechanical mapping and modulation in vivo with cellular and subcellular resolution. Key innovations will include a bioinspired three-dimensional sensor–actuator network, lattice light-sheet microscopy with adaptive optics, and a computational analysis pipeline, which will be applied to study zebrafish morphogenesis. These technologies will provide new capabilities to probe and perturb biomechanics in living organisms, advancing tissue engineering, regenerative medicine, and biomaterials research. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria. NSF Award ID: 2543120 | Program: 01002627DB NSF RESEARCH & RELATED ACTIVIT | Principal Investigator: Tian-Ming Fu | Institution: Princeton University, PRINCETON, NJ | Award Amount: $600,000 View on NSF Award Search: https://www.nsf.gov/awardsearch/show-award/?AWD_ID=2543120 View on Research.gov: https://www.research.gov/awardapi-service/v1/awards/2543120.html