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

Area of Science:

• Pulmonary Medicine
• Biophysics
• Cellular Mechanics

Background:

• Airway smooth muscle (ASM) contraction drives acute bronchospasm in asthma.
• Current methods study ASM in isolation, lacking native airway context.
• Limitations exist in sensitivity, variability, and spatial data of existing techniques.

Purpose of the Study:

• Introduce tissue traction microscopy (TTM) for measuring ASM contractile force in precision-cut lung slices (PCLS).
• Compare TTM to conventional methods for assessing ASM activity in PCLS.
• Investigate ASM force dynamics and identify localized contraction regions.

Main Methods:

• Developed and applied tissue traction microscopy (TTM) on porcine and human PCLS.
• Measured ASM contractile force directly within the lung tissue microenvironment.
• Compared TTM force measurements with conventional lumen area changes.

Main Results:

• TTM is more sensitive to bronchoconstrictor stimuli than lumen area changes.
• TTM exhibits less variability across different airways.
• TTM provides crucial spatial information, revealing "stress hotspots" of high ASM contraction.
• Stress hotspots demonstrated dynamic changes in response to cyclic stretch, including fluidization and resolidification.

Conclusions:

• TTM enables direct, precise measurement of ASM force within intact lung tissue.
• TTM offers superior sensitivity, reduced variability, and spatial insights compared to conventional methods.
• This novel platform will accelerate preclinical research on airway reactivity and asthma.
• Identified dynamic stress hotspots provide new insights into ASM behavior.