A light-sheet microscopy (LSM)-based, spatially-resolved 3D dynamic mechanical analysis (DMA) instrument for developmental biology and physiology

University Of Connecticut, Storrs CT

Investigators

Abstract

An award is made to the University of Connecticut to develop an instrument and method that integrate light-sheet microscopy (LSM) and dynamic mechanical analysis (DMA) to characterize the dynamic mechanical properties of live tissues and organs. The instrument's capability to quantify the process of tissue development will greatly advance the study of developmental biology and physiology. The measurement of tissue material properties will also provide vital information to neurobiology, cardiovascular biology, and research on aging because the functions of any organ system are correlated to its structural characteristics. The instrument will be built on an open-source platform, making it widely accessible to the scientific community. This project aims to demonstrate the applicability of the instrument through the analysis of three animal models widely used in biology, namely, Drosophila, zebrafish, and mouse. The time-course 3D visualization of tissue and organ development enabled by the instrument will promote the public understanding of health issues such as infertility, embryonic diseases, and cancer progression. The development of the instrument will also lead to the design of low-cost tools for K-12 education, which will benefit underrepresented racial and ethnic minorities who have limited access to engineering education. LSM is an emerging technology that enables 3D imaging of live biological samples with high temporal and spatial resolution over a long time period. It allows observation of whole organ/tissue development and high-resolution tracking of cell differentiation and migration. DMA is widely used in industry, science, and engineering to characterize the viscoelastic properties of polymers and biomaterials. The project's innovation is the integration of a miniature robotic precision manipulator and image-based 3D structural analysis that combines the benefits of LSM and DMA and creates a novel instrument capable of spatially-resolved dynamic mechanical analysis of growing tissues and organs. During organ development, physical forces push or pull tissues. Dynamic tissue material properties define how tissues respond to those applied forces and control the formation of organ shapes. Although the mechanisms of cellular forces are well studied, the role of tissue material properties on morphogenesis is yet to be studied. The instrument will be capable of measuring both dynamic material properties and forces, providing vital information for studying one of the most fundamental questions in biology: "how are organs shaped?" through whole-organ 3D analysis that is difficult with conventional methods 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.