Modulation of Nuclear Shape by Substrate Rigidity
Department of Cell and Developmental Biology
Biomaterials | Cell Biology | Molecular, Cellular, and Tissue Engineering
The nucleus is mechanically coupled to the three cytoskeletal elements in the cell via linkages maintained by the LINC complex (for Linker of Nucleoskeleton to Cyto-skeleton). It has been shown that mechanical forces from the extracellular matrix (ECM) can be transmitted through the cytoskeleton to the nuclear surface. Here we quantified nuclear shape in NIH 3T3 fibroblasts on polyacrylamide gels with a controlled degree of cross-linking. On soft substrates with a Young's modulus of 0.4 kPa, the nucleus appeared rounded in its vertical cross-section, while on stiff substrates (308 kPa), the nucleus appears more flattened. Over-expression of dominant negative Klarsicht ANC-1 Syne Homology (KASH) domains, which disrupts the LINC complex, eliminated the sensitivity of nuclear shape to substrate rigidity; myosin inhibition had similar effects. GFP-KASH4 over-expression altered the rigidity dependence of cell motility and cell spreading. Taken together, our results suggest that nuclear shape is modulated by substrate rigidity-induced changes in actomyosin tension, and that a mechanically integrated nucleus-cytoskeleton is required for rigidity sensing. These results are significant because they suggest that substrate rigidity can potentially control nuclear function and hence cell function.
LINC complex, Mechanosensing, Nucleus, Polyacrylamide gels, Substrate rigidity
DOI of Published Version
Lovett, D.B., Shekhar, N., Nickerson, J.A., Roux, K.J., and Lele, T.P. (2013). Modulation of Nuclear Shape by Substrate Rigidity. Cell Mol Bioeng 6(2), 230-238. DOI 10.1007/s12195-013-0270-2. Link to article on publisher's website
Cellular and Molecular Bioengineering
Lovett, David B.; Shekhar, Nandini; Nickerson, Jeffrey A.; Roux, Kyle J.; and Lele, Tanmay P., "Modulation of Nuclear Shape by Substrate Rigidity" (2013). Nickerson Lab Publications. 8.