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Oxford researchers have used advanced microscopy techniques to measure previously unseen forces generated by cells during an immune response; a breakthrough for mechanobiology and future advances in health and disease.

Images from 2D TIRF-SIM-TFM and aTFM microscopic methodologies.
Images from 2D TIRF-SIM-TFM and aTFM microscopic methodologies.

Two recent publications from the Biophysical Immunology Lab, led by Prof Fritzsche at the Rosalind Franklin Institute and Kennedy Institute of Rheumatology at the University of Oxford, have established novel methodologies to measure the small forces occurring in immune cells during an immune response.

The work, led by Dr. Huw Colin-York and Liliana Barbieri in Prof Marco Fritzsche's group, develops and applies new force probing methodologies by combining traction force microscopy and the unique TIRF-SIM technology established between the Fritzsche and Dustin groups in close collaboration with Prof Dong Li (Institute of Biophysics at the Chinese Academy of Science) and Prof Eric Betzig (HHMI Janelia, Noble Laureate in chemistry 2014) at the Kennedy. 

Quantifying small, rapidly evolving forces generated by cells of the immune system is a major challenge for the understanding of biomechanics and mechanobiology in health and disease. The establishment of the two force probing methods allows for measurement of small forces on the pico-Newton range at unprecedented sensitivity in 2D and 3D.

Prof Fritzsche says: "These methods offers a combination of spatio-temporal resolution enhancement relevant to forces on the nano- and sub-second scales, opening up new aspects of mechanobiology of the immune response to analysis."

The study was carried out in close collaboration with Prof Dustin at the Kennedy Institute and Prof Emad Moendarbary's group at UCL and was published in two papers in Nature Communications earlier this month.

Li D*, Colin-York H*, Barbieri L*, Javanmardi Y, Guo T, Korobchevskaya K, Moendarbary E, Li D, Fritzsche M, Astigmatic Traction force microscopy (aTFM), Nature Communications, 2021 (*co-first authors). 

Barbieri L*, Colin-York H*, Korobchevskaya K*, Li D, Karedla N, Schneider F, Dustin M, Li D, Fritzsche M, Two-dimensional TIRF-SIM Traction Force Microscopy (2D TIRF-SIM-TFM), Nature Communications, 2021 (*co-first authors). 

Korobchevskaya K, Colin-York H, Barbieri L, Fritzsche M, Extended mechanical force measurements using structured illumination microscopyPhilosophical Transactions Royal Society A, 2021. 

Find out more about the microscope technology