Characterizing chromatin packing scaling in whole nuclei using interferometric microscopy

Chromatin is the macromolecular assembly containing the cell's genetic information, and its architectural conformation facilitates accessibility to activation sites and thus gene expression. We have developed an analytical framework to quantify chromatin structure with spectral microscopy. Chromatin structure can be described as a mass fractal, with packing scaling D up to specific genomic length scales. Considering various system geometries, we established a model to measure D with the interferometric technique partial wave spectroscopy (PWS) and validated the analysis using finite difference time domain to simulate the PWS system. Calculations of D were consistent with ground truth electron microscopy measurements, enabling a high-throughput, label-free approach to quantifying chromatin structure in the nanometer length scale regime.