New imaging approach visualizes how applying force to proteins alters complex formations

Most researchers today understand biology through the principles of biochemistry. Cells communicate and activate processes via chemical signals, and traditional medicine has long focused on how to treat disease by modifying those signals.

Phys.org

A remarkable mechanism for #DisturbedFlow disruption of #EndothelialCell Junction in #Atherosclerosis

Disturbed Flow-activated GRK2 phosphorylates #Vinculin Ser721-> a closed conformation of Vinculin
->⏬VE-cad junction

Dr. Jeng-Jiann Chiu lab Euro Heart J 2022
https://academic.oup.com/eurheartj/advance-article/doi/10.1093/eurheartj/ehac647/6830649

Vinculin phosphorylation impairs vascular endothelial junctions promoting atherosclerosis

AbstractBackground and aims. Atherosclerosis preferentially develops in arterial branches and curvatures where vascular endothelium is exposed to disturbed flow

OUP Academic
"Single-molecule magnetic tweezers to capture over a million individual transitions as a single talin protein unfolds and refolds under force in equilibrium. When observed at classically probed timescales, talin folds in an apparently uncomplicated two-state manner. As the sampling time extends from minutes to days, the underlying energy landscape exhibits gradually larger signatures of complexity, involving a finite number of well-defined rare conformations.[...]The physiological relevance of each distinct conformation can be connected to the binding of the cytoskeletal protein vinculin, suggesting an extra layer of complexity in talin-mediated mechanotransduction."
https://www.nature.com/articles/s41567-022-01808-4
#StructuralBiology #Talin #Vinculin #MechanoTransduction #MechanoBiology #Cytoskeleton
Enhanced statistical sampling reveals microscopic complexity in the talin mechanosensor folding energy landscape - Nature Physics

Single-molecule magnetic tweezers enable probing the folding dynamics of a single talin protein for long periods of time. This allows the observation of previously inaccessible rare and kinetically trapped conformations.

Nature