Unique Mechanical Properties of Cell Nuclei Regulated by Chromatin

Abstract

Nuclear mechanics and structure could affect gene regulation and gene expression. Chromatin, a major component of cell nuclei, could play an important role in maintaining nuclear integrity and their mechanical properties. Previous studies on nuclear mechanical properties have focused largely on the role of the nuclear lamina, using techniques such as AFM and micropipette aspiration. In this work, we explicitly address the contributions of chromatin to nuclear rheology after isolation from the cell using a microfluidic optical stretcher. We find that isolated nuclei swell in volume under uni-axial stress and exhibit significant softening with increased nuclear size, which can be described by a filtration model for the nuclear membrane and a cortical chromatin model, respectively. In addition, changes to the state of chromatin condensation via histone modifications or chromatin remodeling processes (ATP, topoisomerase II) can strongly impact nuclear morphology and compliance. Moreover, isolated nuclear mechanics is also sensitive to ionic conditions: nuclei stiffen with increasing ionic strength of the buffer and exhibit a transition from stretch to contraction in the presence of multivalent ions (only). Finally, we find that in contrast to other studies suggesting a high refractive index of cell nuclei compared to the cytoplasm, the refractive index of isolated cell nuclei of a variety of cell types can be lower than the refractive index of the cells. The presented work establishes a quantitative link between nuclear mechanical properties and the compaction state of chromatin, which can be modulated by a change in nuclear volume, chromatin remodeling or electrochemical environment.