Mechanical activation of TRP channels by force-from-filament mechanisms and their coupling to Piezo1

• Applicant: Dr. Tabea Caroline Fricke
• Subject Area: Anatomy and Physiology ; Anaesthesiology
• Term: since 2026
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 577614085

Cells in the human body are constantly exposed to mechanical stimuli such as stretching, pressure, or shear forces. In order to perceive these stimuli and convert them into biological signals, they possess specialized proteins known as mechanosensitive ion channels. These channels control important processes such as touch perception, cell differentiation, and immune responses. Despite their central importance, little is known about how exactly these channels recognize and process mechanical information. The proposed research project aims to fundamentally reexamine the mechanosensory function of a specific family of such ion channels, known as TRP channels. Two complementary hypotheses will be tested: 1. TRP channels act as primary mechanosensors that are specifically activated via cellular contact points such as the cytoskeleton or the extracellular matrix (“force-from-filament”) – in contrast to classical membrane stretching. 2. TRP channels are secondarily activated by other mechanosensitive channels such as Piezo1, thereby amplifying or modulating mechanical signals (“mechanoamplification”). The aim is to find out which of these mechanisms are physiologically relevant and how they influence cellular responses to mechanical stimuli – e.g., in tissues subject to high mechanical stress. The project will focus on investigating the role of Piezo1 and TRPV2 in cardiac fibroblasts and analyzing their contribution to differentiation into myofibroblasts – a key process in pathological remodeling processes such as fibrosis. In addition to siRNA-based knockdowns, functional analyses (calcium imaging, mechanical stimulation, gene expression analyses) and protein biochemical methods (e.g., co-immunoprecipitation) will be used. The results should enable a new understanding of mechanosensitive signal processing – with potential relevance for basic research as well as for pathophysiological mechanisms in heart disease.

• DFG Programme: WBP Fellowship
• International Connection: Australia
• Host: Professor Boris Martinac, Ph.D.