Joe Swift: Nuclear Lamin-A scales with tissue stiffness and enhances matrix- directed differentiation
1st of April 2015, Chichley Hall
Joe Swift talked about work he did in the lab of Dennis Discher on the use of proteomics to untangle the influences that lamin mutations have on cell mechanics.
Lamins are a group of proteins that line the inner aspect of the nuclear membrane. They belong to the intermediate filament family of proteins and form part of the mechanical linkage between the cytoskeleton and the DNA spooled up within the chromosomes mechanically to the cytoskeleton and thus the outside world. These proteins are responsive to the mechanical environment and the relative amount of lamin-A (a subtype) that is present within the nucleus scales with the mechanical properties of the tissue: the stiffer a tissue, the more lamin-A is present. Mutations to lamin-A that cause a range of hereditary diseases (termed laminopathies) lead to changes in the mechanical properties of nuclei, making them less resilient to the application of external forces. Joe showed how he had developed a method to label cysteines that were typically buried within folded proteins, but exposed when the proteins were mechanically stressed. The conformation of lamin-A was thus shown to change in nuclei deformed by mechanical challenge. The mechanical properties of tissues are determined largely by the concentration and cross-linking of matrix molecules such as collagen, but within cells, the nucleus is protected by lamin-A which is responsive to more demanding environments.
The work here is published e.g. in Science: http://www.sciencemag.org/content/341/6149/1240104.full
Perspective on this in Science: http://www.sciencemag.org/content/341/6149/965.full
Recently Joe moved to the University of Manchester and established his own lab.
More about Joe Swift: http://www.manchester.ac.uk/research/joe.swift/
More about the Discher lab: http://www.seas.upenn.edu/~discher/
The text was refined with the help of Joe Swift.
This talk was part of a workshop on "Cell Mechanobiology" organised by Rene de Borst, which took place April 1st and 2nd 2015, with support by the Royal Society at Chicheley Hall. for the programme details see: http://bio-mat-sketches-mor.blogspot.co.uk/2015/04/cell-mechanobiology-workshop-1st-2nd.html