Does Cell Shape Determine Cell Fate?

Abstract

Different types of cells, i.e. from different tissues, typically look quite different from each other. Even when cultured on two-dimensional surfaces like glass slides or tissue culture polystyrene under identical conditions, cells adopt different shapes. These shapes are in general functions of the cytoskeletal properties of those cells, itself a subset of what we call the “state” of the cell. Moreover the changes in cell shape upon perturbation of the surface or of the cells themselves should reflect their intrinsic cellular properties, i.e. the cell state. Significant evidence has accumulated that changes in shape can also alter cellular properties, at least for some cells. Our experiments suggest that for Mesenchymal Stem Cells (MSCs), shape perturbations have consequences for their differentiation into osteoblasts. Thus shape seemed linked to fate. These statements beg the question: is it possible to use cell shape to assess cell state? For example can we back-calculate the cytoskeletal properties of the cell from the way it looks on surfaces? This question becomes all the more interesting for cancer cells since cancer cells are known to have altered mechanical properties compared to normal cells, and invasive cancer cells appear to have altered mechanical properties compared to non-invasive cancer cells. In this work we present a combination of experiments and statistical data analysis to try to begin to understand how cell shapes are affected by changes in surface properties or by perturbations of the cytoskeleton. We use fluorescent imaging to obtain the two-dimensional profile of cells and novel Third Harmonic Generation methods to obtain three-dimensional images on cells on substrates. We use these experiments to infer how the cell shape of cancer cells could be associated with their invasive properties. We discuss some rudimentary mathematical models based on these results.