Tissue traction microscopy to quantify muscle contraction within precision-cut lung slices

Sumati Ram-Mohan; Yan Bai; Niccole Schaible; Allen J Ehrlicher; Daniel P Cook; Bela Suki; David A Stoltz; Julian Solway; Xingbin Ai; Ramaswamy Krishnan

doi:10.1152/AJPLUNG.00297.2019

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Tissue traction microscopy to quantify muscle contraction within precision-cut lung slices

Journal article

Open access

Peer reviewed

Tissue traction microscopy to quantify muscle contraction within precision-cut lung slices

Sumati Ram-Mohan, Yan Bai, Niccole Schaible, Allen J Ehrlicher, Daniel P Cook, Bela Suki, David A Stoltz, Julian Solway, Xingbin Ai and Ramaswamy Krishnan

American journal of physiology. Lung cellular and molecular physiology, Vol.318(2), pp.L323-L330

02/01/2020

DOI: 10.1152/AJPLUNG.00297.2019

PMCID: PMC7052683

PMID: 31774304

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Abstract

In asthma, acute bronchospasm is driven by contractile forces of airway smooth muscle (ASM). These forces can be imaged in the cultured ASM cell or assessed in the muscle strip and the tracheal/bronchial ring, but in each case, the ASM is studied in isolation from the native airway milieu. Here, we introduce a novel platform called tissue traction microscopy (TTM) to measure ASM contractile force within porcine and human precision-cut lung slices (PCLS). Compared with the conventional measurements of lumen area changes in PCLS, TTM measurements of ASM force changes are ) more sensitive to bronchoconstrictor stimuli, ) less variable across airways, and ) provide spatial information. Notably, within every human airway, TTM measurements revealed local regions of high ASM contraction that we call "stress hotspots". As an acute response to cyclic stretch, these hotspots promptly decreased but eventually recovered in magnitude, spatial location, and orientation, consistent with local ASM fluidization and resolidification. By enabling direct and precise measurements of ASM force, TTM should accelerate preclinical studies of airway reactivity.

Animals

Animals, Newborn

Biomechanical Phenomena

Bronchoconstriction - physiology

Humans

Lung - physiology

Microscopy

Muscle Contraction - physiology

Muscle, Smooth - physiology

Stress, Mechanical

Swine

Traction

Details

Title: Subtitle: Tissue traction microscopy to quantify muscle contraction within precision-cut lung slices
Creators: Sumati Ram-Mohan - Beth Israel Deaconess Medical Center
Yan Bai - Brigham and Women's Hospital
Niccole Schaible - Beth Israel Deaconess Medical Center
Allen J Ehrlicher - McGill University
Daniel P Cook - University of Iowa
Bela Suki - Boston University
David A Stoltz - University of Iowa
Julian Solway - University of Chicago
Xingbin Ai - Brigham and Women's Hospital
Ramaswamy Krishnan - Beth Israel Deaconess Medical Center
Resource Type: Journal article
Publication Details: American journal of physiology. Lung cellular and molecular physiology, Vol.318(2), pp.L323-L330
DOI: 10.1152/AJPLUNG.00297.2019
PMID: 31774304
PMCID: PMC7052683
NLM abbreviation: Am J Physiol Lung Cell Mol Physiol
ISSN: 1040-0605
eISSN: 1522-1504
Grant note: UH3 HL123816 / NHLBI NIH HHS P01 HL091842 / NHLBI NIH HHS R21 HL123522 / NHLBI NIH HHS K08 HL135443 / NHLBI NIH HHS T32 GM007337 / NIGMS NIH HHS
Language: English
Date published: 02/01/2020
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Molecular Physiology and Biophysics; Pulmonary, Critical Care, and Occupational Medicine; Internal Medicine
Record Identifier: 9984297604302771

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