Mechanobiology of Chromatin and the Nuclear Interior

Abstract

The view of the cell nucleus has evolved from an isolated, static organelle to a dynamic structure integrated with other mechanical elements of the cell. Both dynamics and integration appear to contribute to a mechanical regulation of genome expression. Here, we review physical structures inside the nucleus at different length scales and the dynamic reorganization modulated by cellular forces. First, we discuss nuclear organization focusing on self-assembly and disassembly of DNA structures and various nuclear bodies. We then discuss the importance of connections from the chromatin fiber through the nuclear envelope to the rest of the cell as they relate to mechanobiology. Finally, we discuss how cell stimulation, both chemical and physical, can alter nuclear structures and ultimately cellular function in healthy cells and in some model diseases. The view of chromatin and nuclear bodies as mechanical entities integrated with force generation from the cytoskeleton combines polymer physics with cell biology and medicine.

Keywords: Chromatin; Genome expression; Laminopathy; Nuclear mechanics; Nucleoskeleton; Reptation; Self-assembly.

FIGURE 1

Nuclear structural changes that impact gene expression. Forces generated in the cell from actin-myosin or from outside of the cell are transmitted by cytoskeleton-LINC-nucleoskeleton connections to the chromatin. Force induced movements within the nucleus cause or enhance the following structural changes and regions of anomalous flux. This may lead to (i) altered dynamics of transcription factories and improved accessibility of proteins in these regions; (ii) decondensation of chromatin directly by mechano-modulation and indirectly through biochemical pathways; and (iii) altered stability and assembly of subnuclear bodies including nucleoli.