Regensburg 2025 – wissenschaftliches Programm
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BP: Fachverband Biologische Physik
BP 25: Cell Mechanics II
BP 25.3: Vortrag
Donnerstag, 20. März 2025, 10:15–10:30, H44
Environmental stiffness regulates neuronal maturation via Piezo1-mediated TTR activity — •Eva Kreysing1,2,3, Hélène Gautier1, Leila Muresan1, Sudipta Mukherjee1,2,3, Alexander Winkel1, Xiaohui Zhao1, Ragnhildur Thóra Káradóttir1, and Kristian Franze1,2,3 — 1University of Cambridge, UK — 2FAU Erlangen — 3MPZ Erlangen
During the development of the nervous system, neurons grow axons and dendrites to connect with other cells. As neurons become integrated into the neural network, they mature and develop electrical activity. While mechanical interactions between neurons and their environment are critical for axon growth and pathfinding, the role of mechanical cues in the electrical maturation of neurons, and thus the formation of circuits in the developing brain, remain unexplored. Here, we cultured rat hippocampal neurons on substrates with different mechanical properties and found that electrical activity developed earlier on soft hydrogels compared to stiff hydrogels. This stiffness-dependent neuronal maturation was mediated by the mechanosensitive ion channel Piezo1. Using RNA sequencing, pathway analysis and Western blots, we identified a downstream signalling cascade responsible for the differential expression of neurotransmitter receptors. Finally, we found that stiffening of the developing Xenopus brain leads to impaired synapse formation in vivo. Our findings highlight the critical role of mechanical signals in neuronal maturation and suggest that local brain tissue stiffness is a critical parameter for circuit formation in the developing brain.
Keywords: Neuronal maturation; Environmental stiffness