Non-FAU Project
Start date : 01.07.2019
End date : 30.06.2022
The heart transforms electrical signals into mechanical action to continuously pump blood through our circulation. In reverse, mechanical stimuli during active contraction or passive filling distention are sensed and modulate electrical signals through so called cardiac mechano-electric feedback (MEF)[1]. The MEF involves complex activation of mechanical biosensors initiating short-term and long-term effects through Ca2+ signals in cardiomyocytes in acute and chronic pressure overload scenarios (e.g. heart failure). How mechanical forces alter cardiac function at the molecular level remains unknown. In this innovative project, we aim to study how defined mechanical stimuli (stress) deform the cell membrane (strain) leading to activation of mechanosensitive channels (MSC), including the recently discovered family of Piezo channels[3] suspected to play a major role in development of cardiac hypertrophy and heart failure[2]. We will first focus on the murine immortalised atrial cardiomyocytes HL-1 cell line to investigate Ca2+ signalling through aberrantly activated MSC and subsequent MEF before studying mammalian adult ventricular cardiomyocytes. One part of this international collaborative project consists in redesigning an existing IsoStretcher biomechatronics system[4] into a next generation MultiStretcher system for scaling up high-content screening of cellular signalling pathways and control of biological batch-to-batch variation. While the engineering of this parallelized MultiStretcher will be carried out at the institution (Medical Biotechnology Institute at Friedrich Alexander University, FAU, Erlangen-Nürnberg) by the team of Prof Oliver Friedrich, our long-standing collaborator and international co-investigator on this project, the application of the Iso- and MultiStretcher for investigations of MEF-related cell biology and pharmacology will be carried out at the Victor Chang Cardiac Research Institute (VCCRI). The system technology will be transferred to VCCRI for the ongoing support of cardiac mechanotransduction research.