Regensburg 2019 – wissenschaftliches Programm

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BP: Fachverband Biologische Physik

BP 31: Cell adhesion and migration, multicellular systems II

BP 31.9: Vortrag

Freitag, 5. April 2019, 11:45–12:00, H10

Coiled coils as molecular force sensors for the extracellular matrix — •Melis Goktas, Chuanfu Luo, Ruby May Arana Sullan, Ana Elisa Bergues-Pupo, Reinhard Lipowsky, Ana Vila Verde, and Kerstin Blank — Max Planck Institute of Colloids and Interfaces, Science Park Potsdam-Golm, 14424 Potsdam, Germany.

Cells sense the mechanical properties of the extracellular matrix (ECM) and use this information for regulating a wide range of cellular functions. Even though it is well understood that mechanical signals play a crucial role in directing cell fate, surprisingly little is known about the range of forces that define cell-ECM interactions at the molecular level. To determine the single molecular forces required to maintain initial cell adhesion, we developed a library of coiled coil (CC)-based molecular force sensors (MFSs). Using AFM-based SMFS, we have calibrated the rupture forces of a series of short heterodimeric CCs (3-5 heptad repeats) under shear geometry. We show that the rupture forces lie in the range of 20-50 pN and depend on CC length (i.e. number of heptads). Using these mechanically calibrated CCs as molecular building blocks, we developed a two-component MFS approach. Proof-of-concept experiments performed with fibroblasts and endothelial cells revealed that single integrin-ligand bonds transmit forces lower than 40 pN during initial cell adhesion and that cells with endothelial lineage exert lower cell-ECM forces compared to fibroblasts. These results aid the future design of 2D and 3D CC-based MFS platforms for investigating cellular mechanosensing processes at the single molecule level.