BPCPPDYSOE21 – scientific programme

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BP: Fachverband Biologische Physik

BP 16: Single Molecule Biophysics II

BP 16.2: Talk

Tuesday, March 23, 2021, 11:20–11:40, BPa

Magnetic Tweezers Protein Force Spectroscopy: Applications to Von Willebrand Factor and SARS-CoV-2 Cell Adhesion — •Jan Lipfert¹, Magnus Bauer¹, Steffen Sedlak¹, Achim Löf¹, Tobias Obser², Maria Brehm², Martin Benoit¹, Adina Hausch¹, and Sophia Gruber¹ — ¹Department of Physics, LMU Munich — ²Department of Pediatric Hematology and Oncology, University Medical Center Hamburg Eppendorf

The physiological function of proteins is often critically affected by forces acting on them. We have developed a versatile and modular approach for force measurements on proteins in magnetic tweezers [Löf et al. PNAS 2019; Gruber et al. Nanoscale 2020] that enables ultra-stable (>days) and parallel measurements (>50) in a wide force range, in particular at low forces (<1 pN).

We apply our new assay to two systems critical in human pathologies: the blood protein von Willebrand Factor (VWF) and the Spike-mediated adhesion of SARS-CoV-2, the causative agent of the current pandemic. First, we probe regulatory transitions at low forces within VWF. Our results reveal fast (~250 ms) transitions in the dimeric VWF stem around 1 pN, which likely constitute the first steps in its mechano-activation. Second, we use a tethered ligand assay to quantitate how the SARS-CoV-2 spike protein binds to its cellular receptor ACE2. We find that SARS-CoV-2 has a higher force stability and lower off-rate than the previous SARS-CoV-1, which caused the 2002 pandemic, which might contribute to different infection patterns observed for the two viruses.