Recent advances in understanding nuclear size and shape

Abstract

Size and shape are important aspects of nuclear structure. While normal cells maintain nuclear size within a defined range, altered nuclear size and shape are associated with a variety of diseases. It is unknown if altered nuclear morphology contributes to pathology, and answering this question requires a better understanding of the mechanisms that control nuclear size and shape. In this review, we discuss recent advances in our understanding of the mechanisms that regulate nuclear morphology, focusing on nucleocytoplasmic transport, nuclear lamins, the endoplasmic reticulum, the cell cycle, and potential links between nuclear size and size regulation of other organelles. We then discuss the functional significance of nuclear morphology in the context of early embryonic development. Looking toward the future, we review new experimental approaches that promise to provide new insights into mechanisms of nuclear size control, in particular microfluidic-based technologies, and discuss how altered nuclear morphology might impact chromatin organization and physiology of diseased cells.

Crosshatch nanofiber networks of tunable interfiber spacing induce plasticity in cell migration and cytoskeletal response

“…6B). Previous studies have shown that nuclear shape and size can influence gene transcription and access of transcriptional machinery to DNA (76)(77)(78). Surprisingly, gene families associated with the transcriptional activity are suppressed, and we do not observe dynamic changes concordant with changes in nucleus shape and size observed between cells on the different fiber networks.…”

“…Our current and future studies are aimed at discerning the mechanisms of drug resistance in our in vitro models of thyroid cancer and determining whether growth on varying interfiber spacing changes the sensitivity of tumor cells to molecular inhibitors. Finally, although we did not identify transcriptional and metabolic changes that have been previously reported in regards to nuclear shape changes (76)(77)(78), we cannot exclude the possibility that chronic stresses and strain to nuclear shape associated with repeated cycles of attachment and recoil that were observed may have contributed to some of the transcriptional reprogramming and expression changes observed. We believe short-to long-term future studies using our platform provide novel quantifiable metrics to dissect whether acute nuclear shape changes vs. chronic stresses to nuclear shape associated with motility and recoil forces lead to distinct transcriptional responses.…”

Nuclear parameters and chromatin remodeling in epithelial cells and lymphocytes from the palpebral conjunctiva of dogs with keratoconjunctivitis sicca

“…Nuclear size and shape are important geometric parameters associated with cell integrity and functionality. 18,42 It is likely that changes in the size of the cell nucleus, as seen in this study, result from alterations in vesicular transport of proteins within the endoplasmic reticulum, and in nuclear envelope formation. 18,42,43 Changes in nuclear shape result from the reorganization of the nuclear lamina and are indicative of changes in nuclear stiffness and/or chromatin supraorganization and functionality.…”

“…The median values of STT1 were 25.00 mm/min (range, [16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35] for the control group and 2.90 mm/min (range, 0-9) for the KCS group (P < .001). In relation to the TBUT, the median values were 10.00 seconds (range, 1-25) for the control group and 0.00 second (range, 0-8) for the KCS group (P < .001).…”

“…17 A normal cell maintains its nucleus within a genetically defined size, but an altered cell often exhibits changes in nuclear size and shape. 18 The major component of the nucleus is chromatin, a malleable fiber that results from the assembly of DNA with histones and other nucleoproteins. 1,19,20 The degree of DNA affinity for histones organizes the genome into either open/relaxed (euchromatin) or compacted chromatin (heterochromatin) and thus regulates the accessibility of genes for transcription, replication, and repair.…”