Journal
ADVANCED HEALTHCARE MATERIALS
Volume 7, Issue 14, Pages -Publisher
WILEY
DOI: 10.1002/adhm.201800069
Keywords
airway smooth muscle cells; integrins; mechanopharmacology; molecular tension sensors
Funding
- National Science Foundation [CAREER-1553344]
- National Institutes of Health [R01GM124472, P01HL114471]
- National Cancer Institute Predoctoral to Postdoctoral Fellow Transition Award [F99CA223074]
- National Institute of Environmental Health Science [P30ES13508]
- Emory Integrated Genomics Core (EIGC)
- Emory University School of Medicine
- National Center for Advancing Translational Sciences of the National Institutes of Health [UL1TR000454]
- Atlanta VA Medical Center
- Div Of Molecular and Cellular Bioscience
- Direct For Biological Sciences [1350829] Funding Source: National Science Foundation
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Given that dysregulation of mechanics contributes to diseases ranging from cancer metastasis to lung disease, it is important to develop methods for screening the efficacy of drugs that target cellular forces. Here, nanoparticle-based tension sensors are used to quantify the mechanical response of individual cells upon drug treatment. As a proof-of-concept, the activity of bronchodilators is tested on human airway smooth muscle cells derived from seven donors, four of which are asthmatic. It is revealed that airway smooth muscle cells isolated from asthmatic donors exhibit greater traction forces compared to the control donors. Additionally, the mechanical signal is abolished using myosin inhibitors or further enhanced in the presence of inflammatory inducers, such as nicotine. Using the signal generated by the probes, single-cell dose-response measurements are performed to determine the mechano effective concentration (mechano-EC50) of albuterol, a bronchodilator, which reduces integrin forces by 50%. Mechano-EC50 values for each donor present discrete readings that are differentially enhanced as a function of nicotine treatment. Importantly, donor mechano-EC50 values varied by orders of magnitude, suggesting significant variability in their sensitivity to nicotine and albuterol treatment. To the best of the authors' knowledge, this is the first study harnessing a piconewton tension sensor platform for mechanopharmacology.
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