Title: Response to Comment on "Cell nuclei have lower refractive index and mass density than cytoplasm",
Abstract: In a recent study entitled "Cell nuclei have lower refractive index and mass
density than cytoplasm", we provided strong evidence indicating that the
nuclear refractive index (RI) is lower than the RI of the cytoplasm for several
cell lines. In a complementary study in 2017, entitled "Is the nuclear
refractive index lower than cytoplasm? Validation of phase measurements and
implications for light scattering technologies", Steelman et al. observed a
lower nuclear RI also for other cell lines and ruled out methodological error
sources such as phase wrapping and scattering effects. Recently, Yurkin
composed a comment on these 2 publications, entitled "How a phase image of a
cell with nucleus refractive index smaller than that of the cytoplasm should
look like?", putting into question the methods used for measuring the cellular
and nuclear RI in the aforementioned publications by suggesting that a lower
nuclear RI would produce a characteristic dip in the measured phase profile in
situ. We point out the difficulty of identifying this dip in the presence of
other cell organelles, noise, or blurring due to the imaging point spread
function. Furthermore, we mitigate Yurkin's concerns regarding the ability of
the simple-transmission approximation to compare cellular and nuclear RI by
analyzing a set of phase images with a novel, scattering-based approach. We
conclude that the absence of a characteristic dip in the measured phase
profiles does not contradict the usage of the simple-transmission approximation
for the determination of the average cellular or nuclear RI. Our response can
be regarded as an addition to the response by Steelman, Eldridge and Wax. We
kindly ask the reader to attend to their thorough ascertainment prior to
reading our response.