Integration of magnetic tweezers and traction force microscopy to investigate extracellular matrix microrheology and keratinocyte mechanobiology

In humans, autoimmune bullous diseases (AIBDs) represent a class of chronic and severe acquired skin diseases where the body produces autoantibodies triggering blisters and ulcers in the skin and mucosa. Loss of the mechanical barrier function of skin and mucosa over widespread areas can subsequently lead to opportunistic infections, and in some instances, even death. While the anchoring junctions of epidermal keratinocytes targeted by pathogenic autoantibodies are known for many types of AIBDs, the biophysical mechanisms causing the breakdown of these anchoring junctions remain mostly unknown. Thus, current treatments rely on steroids or immunosuppressants to suppress antibody production and reduce inflammation.

To bridge the mechanistic knowledge gaps of AIBDs, new experimental approaches are needed. To date, there are few fundamental studies of force transmission between epidermal keratinocytes or between keratinocytes and neighboring extracellular matrix. To meet this goal, we developed a new experimental method integrating the well-established techniques of magnetic tweezers (MTs) and traction force microscopy (TFM). The integrated methodology was validated with two proof-of-concept model experiments. The first was where we measured the local mechanical properties of type I collagen, and the second was where we studied force transmission between a keratinocyte and its underlying culture matrix. Together, these two demonstrations suggest that the integrated MT-TFM method will be a useful tool to better understand the missing mechanistic knowledge of AIBDs. Moreover, it is our hope this can start us on the path of developing innovative therapeutics, especially ones designed to strengthen the structural integrity of the epidermis instead of the current adverse immunosuppressive treatments.