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.
Original language | English (US) |
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Pages (from-to) | 11585-11596 |
Number of pages | 12 |
Journal | ACS Nano |
Volume | 15 |
Issue number | 7 |
DOIs | |
State | Published - Jul 27 2021 |
Keywords
- cell contraction
- cell shortening
- focal adhesion
- mechanobiology
- molecular force probe
- muscle biophysics
- tension gauge tether
ASJC Scopus subject areas
- General Materials Science
- General Engineering
- General Physics and Astronomy