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Molecular Tension Probes to Investigate the Mechanopharmacology of Single Cells: A Step toward Personalized Mechanomedicine
Author(s) -
Galior Kornelia,
Ma Victor PuiYan,
Liu Yang,
Su Hanquan,
Baker Nusaiba,
Panettieri Reynold A.,
Wongtrakool Cherry,
Salaita Khalid
Publication year - 2018
Publication title -
advanced healthcare materials
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.288
H-Index - 90
eISSN - 2192-2659
pISSN - 2192-2640
DOI - 10.1002/adhm.201800069
Subject(s) - ec50 , nicotine , chemistry , myosin , biophysics , traction (geology) , pharmacology , medicine , biomedical engineering , in vitro , biology , biochemistry , paleontology
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‐EC 50 ) of albuterol, a bronchodilator, which reduces integrin forces by 50%. Mechano‐EC 50 values for each donor present discrete readings that are differentially enhanced as a function of nicotine treatment. Importantly, donor mechano‐EC 50 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.