Intranuclear strain in living cells subjected to substrate stretching: A combined experimental and computational study

Abstract

Nuclear deformation caused by mechanical stimuli has been suggested to significantly impact various cellular activities, such as gene expression, protein synthesis and mechanotransduction. To understand how nuclear deformation regulates cellular behaviors, the details of intranuclear strain distribution caused by mechanical stimuli as well as intranuclear mechanical properties are required. Here, we examine local mechanical strains within the nucleus in a living cell subjected to substrate stretching and estimate the local nuclear mechanical properties. A HeLa cell in a PDMS chamber was subjected to a 10% step-strain by using a custom-made uni-axial stretching device. Local displacements and the distribution of the equivalent strain within the nucleus were obtained from fluorescence images of the nucleus before and after the application of stretching. The intranuclear strain showed heterogeneous distribution, and higher strain regions were observed not only at the center, but also periphery of the nucleus. We examined the role of the chromatin condensation level and actin cytoskeleton by treating cells with Trichostatin A and Cytochalasin D, respectively. Interestingly, these treatments did not cause significant changes in the intranuclear strain distribution. Referring to the experimental results, we reproduced the nuclear strain distribution in a finite element model to estimate relative distribution of Young's modulus within the nucleus, and observed substantially lower Young’s modulus levels in the peripheral regions of the nucleus relative to those found in the central regions of the nucleus. We reveal heterogeneous strain distribution within the nucleus in a living cell subjected to substrate stretching, and the results provide insights into the importance of heterogeneity of intranuclear mechanical properties.