journal article·2021-07-27Open access

Molecular Nanomechanical Mapping of Histamine-Induced Smooth Muscle Cell Contraction and Shortening

Myung Hyun Jo, Byoung Choul Kim, Keewon Sung, Reynold A. Panettieri, Steven S. An, Jian Liu, Taekjip Ha

ACS Nano· Volume 15· Issue 7

Abstract

Mechanical response to external stimuli is a conserved feature of many cell types. For example, neurotransmitters (e.g., histamine) trigger calcium signals that induce actomyosin-regulated contraction of airway smooth muscle (ASM); the resulting cell shortening causes airway narrowing, the excess of which can cause asthma. Despite intensive studies, however, it remains unclear how physical forces are propagated through focal adhesion (FA)—the major force-transmission machinery of the cell—during ASM shortening. We provide a nanomechanical platform to directly image single molecule forces during ASM cell shortening by repurposing DNA tension sensors. Surprisingly, cell shortening and FA disassembly that immediately precedes it occurred long after histamine-evoked increases in intracellular calcium levels ([Ca2+]i). Our mathematical model that fully integrates cell edge protrusion and retraction with contractile forces acting on FA predicted that (1) stabilization of FA impedes cell shortening and (2) the disruption of FAs is preceded by their strengthening through actomyosin-activated molecular tension. We confirmed these predictions via real-time imaging and molecular force measurements. Together, our work highlights a key role of FA dynamics in regulating ASM contraction induced by an allergen with potential therapeutic implications.
Source: openalex_inverted_index · Quality: baseline

Research context

OpenAlex topics: Cellular Mechanics and Interactions · Force Microscopy Techniques and Applications · thermodynamics and calorimetric analyses

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Department of Biophysics and Biophysical Chemistry, Johns Hopkins School of Medicine, Baltimore, Maryland 21205, United States

Department of Biomedical Engineering, Johns Hopkins University, Baltimore, Maryland 21218, United States

Division of Nano-Bioengineering, Incheon National University, Incheon 22012, South Korea

Department of Chemistry, Seoul National University, Seoul 08826, South Korea

Rutgers Institute for Translational Medicine and Science, The State University of New Jersey, New Brunswick, New Jersey 08901, United States

Department of Pharmacology, Rutgers−Robert Wood Johnson Medical School, The State University of New Jersey, Piscataway, New Jersey 08854, United States

Department of Cell Biology and Center for Cell Dynamics, Johns Hopkins School of Medicine, Baltimore, Maryland 20205, United States

Howard Hughes Medical Institute, Baltimore, Maryland 21205, United States

Funding

NIH Clinical Center · National Research Foundation of Korea · Johns Hopkins University · National Science Foundation · State of Maryland Department of Health and Mental Hygiene · James Buchanan Brady Urological Institute · New Jersey Alliance for Clinical and Translational Science

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