Application of an IsoStretcher biomechatronics platform and engineering of a novel parallelized MultiStretcher technology for studies of cardiac mechano-signaling in HL-1 atrial cardiomyocytes

Non-FAU Project

Project Details

Project leader:
Prof. Dr. Dr. Oliver Friedrich

Contributing FAU Organisations:
Lehrstuhl für Medizinische Biotechnologie

Start date: 01/07/2019
End date: 30/06/2022

Abstract (technical / expert description):

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.

External Partners

Victor Chang Cardiac Research Institute

Last updated on 2019-11-06 at 10:17