Quantifying the Effects of Cell Division on Mass Redistribution Dynamics in Multicellular Clusters using Live Cell Interferometry

Abstract

Cell division is a biomechanical process that both drives and responds to mechanical perturbations. For example, cell division in a confluent monolayer can induce long-range changes in surrounding cells, and the rate of endothelial cell division rate can be modulated by shear forces imposed by external flow. Conventional optical microscopy methods for measuring cell migration during and in response to cell division quantify these events in terms of length and time, or in terms of rate (change in length over time), using phase contrast or fluorescence microscopy. However, a complete mechanical profile of all biophysical parameters also requires measurement of mass, the third fundamental physical property relevant to intracellular biophysics behind length and time, excluding charge and spin which are not applicable to measurements of cell migration. Live cell interferometry (LCI) uses quantitative phase microscopy to measure cell mass, mass accumulation rate, and mass distribution within single cells or multicellular clusters. In previous work we used LCI to quantify the rate of cell migration within colonies, mass redistribution in daughter cells during mitosis, and the spatial coordination of mass motion in multicellular clusters. Here, we employ temporal autocorrelation, which measures the homogeneity of a time-dependent quantity, to measure the rate of change in colony and cell mass distributions over time. Our data show the dynamic nature of mass redistribution throughout the cell cycle and the dependence of this motion on cell division. Combined with measurements of the mass and distribution of mass within single cells or multicellular clusters, LCI therefore enables quantification of the change in energy dissipation rate due to cell division, and also provides a platform for future studies of the mechanics of cell-cell interactions.