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Abstract: FR-PO707

Podocytes Respond to Mechanical Forces to Spatially Orient Their Processes on Glomerular Capillaries

Session Information

Category: Glomerular Diseases

  • 1304 Glomerular Diseases: Podocyte Biology


  • Unnersjö-Jess, David, Uniklinik Koln, Koln, Germany
  • Ramdedovic, Amer, Uniklinik Koln, Koln, Nordrhein-Westfalen, Germany
  • Butt, Linus, Uniklinik Koln, Koln, Nordrhein-Westfalen, Germany
  • Plagmann, Ingo, Uniklinik Koln, Koln, Nordrhein-Westfalen, Germany
  • Höhne, Martin, Uniklinik Koln, Koln, Nordrhein-Westfalen, Germany
  • Blom, Hans, Kungliga Tekniska Hogskolan, Stockholm, Sweden
  • Hackl, Agnes, Uniklinik Koln, Koln, Nordrhein-Westfalen, Germany
  • Schermer, Bernhard, Uniklinik Koln, Koln, Nordrhein-Westfalen, Germany
  • Benzing, Thomas, Uniklinik Koln, Koln, Nordrhein-Westfalen, Germany

It has recently been proposed by our group that the main role of podocyte foot processes is to counteract forces resulting from filtration pressure in order to compress the basement membrane, thereby optimizing sieving properties. We here expand on these models by studying the role of spatial orientation of foot processes on glomerular capillaries.


We apply novel imaging protocols which allow for confocal in-situ 3D imaging of intact glomerular capillaries at a resolution sufficient to resolve foot processes. This allows for analyzing several thousands of podocyte processes and quantitatively determine their spatial orientation with regards to the capillary orientation.


We report the novel finding that podocyte processes display a non-random distribution on glomerular capillaries, which is lost in different types of kidney disease. This finding suggests that the orientation of foot processes is important for the function of the filtration barrier. We further observe a more prominent orientation preference in elongated and more cylindrical capillary segments, where the difference between circumferential and longitudinal wall stress is highest. This strongly indicates that podocytes possess a machinery to regulate and maintain the spatial orientation of their processes based on the forces acting on them.


We consider the various forces that foot processes are exposed to and conclude that the observed orientation of foot processes in parallel with the orientation axis of capillaries is likely to ensure that slit diaphragm molecules (e.g. nephrin, NEPH1) are preferably aligned in parallel with the axis of highest wall stress. This adds further evidence to the theory that foot processes and the slit diaphragm act to mechanically counteract lateral wall stress, but also possesses a mechanosensory machinery for maintaining orientation on capillaries.

New imaging protocols allow for determining the orientation of foot processes based on nephrin staining (green).


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