Non-invasive single cell biomechanical analysis using live imaging datasets

Abstract

The physiological state of a cell is governed by a multitude of processes and can be described by a combination of mechanical, spatial, and temporal properties. Quantifying cell dynamics at multiple scales is essential for comprehensive studies of cellular function, and remains a challenge via traditional end-point assays. We introduce an efficient, non-invasive computational tool that takes, time-lapse images as input to automatically detect, segment, and analyze unlabeled live cells; the program then outputs kinematic cellular shape and migration parameters, while simultaneously measuring cellular stiffness and viscosity. We demonstrate the program's capabilities by testing it on human mesenchymal stem cells (huMSC) induced to differentiate towards osteoblastic (huOB) lineage, and T-lymphocyte cells (T cells) of naïve and stimulated phenotypes. The program detected relative cellular stiffness differences in huMSC and huOB comparable to studies that utilize atomic force microscopy; it further distinguished naïve from stimulated T cells, based on characteristics necessary to invoke an immune response. In summary, we introduce an integrated tool to decipher spatiotemporal and intracellular dynamics of cells, providing a new and alternative approach for cell characterization.