A highly reproducible measurement of airway and vascular reactivity

A powerful tool to measure airway and vascular reactivity  is the human precision cut lung slice (PCLS). To quantify underlying changes, we describe a simpler, faster, and highly-sensitive approach called tissue traction microscopy (TTM).  Applicable to asthma, COPD, and PAH simulated tissues.

How does TTM work?


A) We adhere the PCLS upon a custom elastic substrate prepared in a single- or a multi-well formats.  B) PCLS adhesion does not affect airway reactivity. C) Representative bright-field images and overlaid contraction maps in response to 10−4 M ACh (30 min) and 10−3 M chloroquine (ChQ; 25 min). Scale bar = 500 μm. D) and E): Time-dependent lumen area changes (gray line) and airway contraction changes (black line) in response to 10−4 M ACh followed by 10−3 M ChQ. Compared to lumen airway changes, airway contraction measurements are less variable from airway-to-airways, 
Ram-Mohan et al, Am J Physiol Lung Cell Mol Physiol. 2020 Feb 1;318(2):L323-L330.


The TTM Advantage

More sensitive


Compared to lumen are changes, TTM
measurements are more sensitive to
broncho- and vaso-constrictor and
dilator stimuli

Higher Content


Provide spatial information. Notably, within
every human airway (or vessel), TTM
measurements have revealed local regions
of high smooth muscle contraction that we
call “stress hotspots”. By enabling direct and
precise measurements of these hotspots
together with their physical and biological
origins,  TTM should accelerate preclinical
studies of airway and vascular reactivity.

Innovative

Label-free, non-invasive, rapid
(<5 minutes per PCLS ),
less variable compared to lumen area
changes, and and readily implemented in
a multi-well format.

Statistics

Small

Set-up Cost

<5 mins

Per PCLS

Multi-well

1, 6, 12 or 24 well format

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