Journal
JOURNAL OF CELL SCIENCE
Volume 127, Issue 14, Pages 3005-3015Publisher
COMPANY BIOLOGISTS LTD
DOI: 10.1242/jcs.149203
Keywords
Cell mechanics; Mechanotransduction; Extra-cellular matrix; Nucleus; Nucleoskeleton; Proteostasis
Categories
Funding
- U.S. National Institutes of Health
- U.S. National Science Foundation
- University of Pennsylvania's research centers (Materials Research Science and Engineering
- Nano Science and Engineering
- Nano/Bio Interface)
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How cells respond to physical cues in order to meet and withstand the physical demands of their immediate surroundings has been of great interest for many years, with current research efforts focused on mechanisms that transduce signals into gene expression. Pathways that mechano-regulate the entry of transcription factors into the cell nucleus are emerging, and our most recent studies show that the mechanical properties of the nucleus itself are actively controlled in response to the elasticity of the extracellular matrix (ECM) in both mature and developing tissue. In this Commentary, we review the mechano-responsive properties of nuclei as determined by the intermediate filament lamin proteins that line the inside of the nuclear envelope and that also impact upon transcription factor entry and broader epigenetic mechanisms. We summarize the signaling pathways that regulate lamin levels and cell-fate decisions in response to a combination of ECM mechanics and molecular cues. We will also discuss recent work that highlights the importance of nuclear mechanics in niche anchorage and cell motility during development, hematopoietic differentiation and cancer metastasis, as well as emphasizing a role for nuclear mechanics in protecting chromatin from stress-induced damage.
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