How a phase image of a cell with nucleus refractive index smaller than that of the cytoplasm should look like?: A Comment on two papers by Steelman et al. and Schürmann et al. Read the Responses to this Comment: e201800091 and e201800095.

In recent papers Steelman et al. ("Is the nuclear refractive index lower than cytoplasm? Validation of phase measurements and implications for light scattering technologies") and Schürmann et al. ("Cell nuclei have lower refractive index and mass density than cytoplasm") obtained quantitative phase images of whole cells of various types and corresponding isolated nuclei and concluded that the refractive index (RI) of the nucleus is significantly smaller than that of the cytoplasm. The comment shows that this conclusion and assumptions used in retrieving the RI necessarily imply a characteristic dip in the center of the whole-cell phase images. This dip is not present in any of the phase images in the discussed papers, which is a strong argument against the conclusion of smaller nucleus RI. It is also discussed whether a different processing of the phase images can help to clarify this issue.