Imaging the Elastic Properties of Cells in 3D Environment

This project aims at characterizing both intracellular and extracellular mechanical properties in 3D cell culture models using novel Brillouin optical microscopy. The biomechanical interaction between cells and their local microenvironment is a crucial regulator of cell function and system level behavior. Most of our current knowledge concerning cell biomechanics came from the studies of 2D monolayers. Although the importance of 3D models have been recognized, it has been difficult to measure the biomechanical parameters, particularly the modulus of elasticity, in 3D cultures. Current standard technologies, such as atomic force microscopy and microrheology, require physical contact between a sample and a probe or are limited to the analysis of few points randomly distributed within a sample. This project will develop and validate Brillouin microscopy and will be used to investigate the differences and similarities in cell mechanical behavior between 3D and 2D microenvironments in various experimental settings relevant to the natural environments in vivo. This study will provide new data-inspired insights into how the dimensionality of cellular microenvironment affects the cells and cell-matrix interactions, and in the process, it will make a novel microscopy modality available in the field of cell biomechanics.

The proposed research involves highly multidisciplinary approaches integrating the cutting edge optical technology and cellular biomechanics and, therefore, will advance both engineering and life sciences. Brillouin cell microscopy is expected to have broader impacts on several research areas, such as tissue engineering and cancer research, beyond cell biomechanics and has the potential for commercialization. Furthermore, this project provides an excellent opportunity to educate and train graduate students and postdoctoral researchers at the interface between engineering and life sciences in a highly interdisciplinary environment at Harvard Medical School and Massachusetts Institute of Technology. Undergraduate students enrolled in the Harvard-MIT Summer Institute for Biomedical Optics and other summer internship programs will be given the opportunity to contribute to this project.