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Elastomeric sensor surfaces for high-throughput single-cell force cytometry
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DOI：10.1038/s41551-018-0193-2.png)
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Abstract
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As cells with aberrant force-generating phenotypes can directly lead to disease, cellular force-generation mechanisms are highvalue targets for new therapies. Here, we show that single-cell force sensors embedded in elastomers enable single-cell force measurements with -100-fold improvement in throughput than was previously possible. The microtechnology is scalable and seamlessly integrates with the multi-well plate format, enabling highly parallelized time-course studies. In this regard, we show that airway smooth muscle cells isolated from fatally asthmatic patients have innately greater and faster force-generation capacity in response to stimulation than healthy control cells. By simultaneously tracing agonist-induced calcium flux and contractility in the same cell, we show that the calcium level is ultimately a poor quantitative predictor of cellular force generation. Finally, by quantifying phagocytic forces in thousands of individual human macrophages, we show that force initiation is a digital response (rather than a proportional one) to the proper immunogen. By combining mechanobiology at the single-cell level with high-throughput capabilities, this microtechnology can support drug-discovery efforts for clinical conditions associated with aberrant cellular force generation.
Keywords:
AIRWAY SMOOTH-MUSCLE
RECEPTOR-MEDIATED PHAGOCYTOSIS
MICROPOST ARRAYS
TRACTION FORCES
FC
CONTRACTION
ACTIVATION
MICROSCOPY
CYTOKINESIS
VITRONECTIN
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