Meshing two techniques to reveal mechanisms underlying immunobullous skin diseases
Meshing two techniques to reveal mechanisms underlying immunobullous skin diseases lead image
Researchers know immunobullous blistering skin diseases result from the body’s production of autoantibodies that target proteins holding the epidermis together. However, the mechanisms underlying the loss of epithelial cell cohesion and blister formation following autoantibody exposure are not fully understood.
Moghram et al. developed a methodology combining two established techniques, magnetic tweezers and traction force microscopy, to study the biophysical mechanisms of immunobullous skin diseases. Three proof-of-concept experiments suggest the integrated methodology will be a valuable tool for mechanobiology.
“We have a very specific application in mind, but I think the real importance of this work is this methodology will allow researchers working in other areas of cell biophysics to ask and answer important questions that expand the state of knowledge in that field,” said author John Selby.
The authors established the fundamentals of this integrated method, determining experimental protocols and methods of data reduction. They described two variants of the methodology, force-control mode and displacement-control mode, and demonstrated each with a simplistic model experiment consisting of a fibronectin-coated superparamagnetic bead attached to a collagen substrate.
The force-control mode experiment showed the method could be used to estimate the elastic storage modulus of the substrate. The displacement-control mode experiment showed the method could be used in experiments requiring large substrate deformations or large forces.
The authors used the force-control mode for a bead-on-cell experiment. They found a force applied to the surface of an isolated human epidermal epithelial cell was transmitted through the cell to the underlying collagen substrate.
The researchers hope to compare force transmission in a sheet of normal interconnected epithelial cells and cells exposed to disease-causing autoantibodies.
Source: “Integration of magnetic tweezers and traction force microscopy for the exploration of matrix rheology and keratinocyte mechanobiology: Model force- and displacement-controlled experiments,” by Waddah I. Moghram, Pratibha Singh, Christian A. VandeLune, Edward A. Sander, and John C. Selby, AIP Advances (2021). The article can be accessed at https://aip.scitation.org/doi/full/10.1063/5.0041262 .
