On the Roles of Actin Stress Fibers on the Mechanical Regulation of Nucleus in Adherent Cells
Actin stress fibers (SFs) play important roles in cellular mechanotransduction and regulation of various cellular functions. SFs generate internal tension and contribute to physical interactions between cells and extracellular matrices. It has recently been suggested that cytoskeletons have the potential to interact with the nuclei via nuclear membrane proteins. However, it remains unclear at this stage whether SFs are involved in a mechanical interaction with the nucleus, and their internal forces are transmitted directly to the nucleus and influence the intranuclear DNA.
Here we investigated the roles of SFs on the mechanical regulation of the nucleus in vascular smooth muscle cells (SMCs) on a substrate. We microdissected apical stress fibers (ASFs) running across the top surface of nucleus or basal stress fibers (BSFs) underneath the nucleus by using a laboratory- built laser nano-scissor and observed the subsequent mechanical responses of the SFs and the nucleus. Shortening of the dissected fibers was significantly greater in the ASFs than in the BSFs. Nuclei also moved in the direction of retraction of the dissected fibers, and displacement of the nucleus was more remarkable after the dissection of the ASFs than after that of the BSFs. These results indicate that ASFs over the nucleus stabilize the position of the nucleus, and that the internal tension of SFs significantly affects nuclear movement. A line-like concentration of intranuclear DNA along ASFs was often observed near the upper surface of the nucleus. These line-like structures of DNA disappeared and changed markedly following the dissection and shortening of ASFs. Interestingly, the dissected ASFs reorganized near their original location in several tens of minutes following ASF dissection in some cases. Intranuclear DNA also aggregated along the reorganized ASFs and aligned in the direction of the fibers. These dynamic realignments of DNA along the reorganized ASFs may be due to interactions between SFs and perinuclear DNA. This interaction may play a role in the stabilization and positional memory of DNA in the nucleus.
KeywordsCell biomechanics Chromatin Force transmission Mechanotransduction
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