title: Cellular Biomechanics in Drug Screening and Evaluation: Mechanopharmacology.
abstract: The study of mechanobiology is now widespread. The impact of cell and tissue mechanics on cellular responses is well appreciated. However, knowledge of the impact of cell and tissue mechanics on pharmacological responsiveness, and its application to drug screening and mechanistic investigations, have been very limited in scope. We emphasize the need for a heightened awareness of the important bidirectional influence of drugs and biomechanics in all living systems. We propose that the term 'mechanopharmacology' be applied to approaches that employ in vitro systems, biomechanically appropriate to the relevant (patho)physiology, to identify new drugs and drug targets. This article describes the models and techniques that are being developed to transform drug screening and evaluation, ranging from a 2D environment to the dynamic 3D environment of the target expressed in the disease of interest.
authors.affiliation: Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
authors.forename: Ramaswamy
authors.initials: R
authors.lastname: Krishnan
authors.affiliation: Harvard T.H. Chan School of Public Health, Boston, MA, USA.
authors.forename: Jin-Ah
authors.initials: JA
authors.lastname: Park
authors.affiliation: Center for Heart Lung Innovation, St Pauls Hospital, University of British Columbia, Vancouver, Canada.
authors.forename: Chun Y
authors.initials: CY
authors.lastname: Seow
authors.affiliation: Department of Mechanical Engineering, University of Melbourne, Melbourne, Australia.
authors.forename: Peter V-S
authors.initials: PV
authors.lastname: Lee
authors.affiliation: Lung Health Research Centre, Department of Pharmacology and Therapeutics, University of Melbourne, Melbourne, Australia. Electronic address: astew@unimelb.edu.au.
authors.forename: Alastair G
authors.initials: AG
authors.lastname: Stewart
mesh_terms: D001696:Biomechanical Phenomena / Q000502:physiology*; D002468:Cell Physiological Phenomena / Q000187:drug effects / Q000502:physiology; D019245:Compressive Strength; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D006801:Humans; D010600:Pharmacology / Q000379:methods*; D033081:Shear Strength; D013718:Tensile Strength
keywords: drug screening; mechanobiology; stiffness; strain; stress; traction