期刊
NATURE PHOTONICS
卷 8, 期 9, 页码 710-715出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/NPHOTON.2014.165
关键词
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资金
- Laser Microbeam and Medical Program, a National Biomedical Technology Resource - National Institutes of Health [P41-EB015890]
- National Science Foundation through the Integrative Graduate Education and Research Traineeship (IGERT) Program [DGE-1144901]
- UC Irvine through the I3 Award Program
We introduce an optical platform for rapid, high-throughput screening of exogenous molecules that affect cellular mechanotransduction. Our method initiates mechanotransduction in adherent cells using single laser-microbeam generated microcavitation bubbles without requiring flow chambers or microfluidics. These microcavitation bubbles expose adherent cells to a microtsunami, a transient microscale burst of hydrodynamic shear stress, which stimulates cells over areas approaching 1 mm(2). We demonstrate microtsunami-initiated mechanosignalling in primary human endothelial cells. This observed signalling is consistent with G-protein-coupled receptor stimulation, resulting in Ca2+ release by the endoplasmic reticulum. Moreover, we demonstrate the dose-dependent modulation of microtsunami-induced Ca2+ signalling by introducing a known inhibitor to this pathway. The imaging of Ca2+ signalling and its modulation by exogenous molecules demonstrates the capacity to initiate and assess cellular mechanosignalling in real time. We utilize this capability to screen the effects of a set of small molecules on cellular mechanotransduction in 96-well plates using standard imaging cytometry.
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