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SKM 2023 – wissenschaftliches Programm

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BP: Fachverband Biologische Physik

BP 4: Tissue Mechanics I

BP 4.4: Vortrag

Montag, 27. März 2023, 15:45–16:00, BAR Schö

'Forcing' changes in health and disease: New access into bioengineered skeletal muscle mechanics for preclinical screening — •Arne Hofemeier1,2, Till Muenker2, Mariam Ristau2, Timo Betz2, and Wolfram Zimmermann11University Medical Center, Göttingen, Germany — 2Third Institute of Physics, Göttingen, Germany

Mechanical properties of skeletal muscles are tightly related to proper functionality, which makes experimental access to the biomechanics of skeletal muscle tissue essential to advance our understanding of muscle function, development and disease. Recently devised in vitro culture systems allow for raising 3D muscle tissues using single cells from patients. However, these systems are inherently incompatible with high resolution microscopy and precise mechanical in-plate measurements. Here, we present a new chamber design that allows real-time high resolution 3D microscopy and non-invasive quantification of global contractile forces and tissue tension during muscle formation. Surprisingly, we found that bioengineered muscles, derived from patients suffering from Duchenne muscular dystrophy, develop under higher tension although they appear weaker upon stimulation. Duchenne is caused by loss of a membrane linker protein, dystrophin, which we therefore dedicate an important novel role as a molecular tension sensor. Testing an individualized gen therapy for a subset of Duchenne patients, we were able to demonstrate that not just the contractile strength of the bioengineered muscles was restored, but also the elevated tissue tension was decreased again.

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