Single molecule mechanics resolves the earliest events in force generation by cardiac myosin
Key steps of cardiac mechanochemistry, including the force-generating working stroke and the release of phosphate (Pi), occur rapidly after myosin-actin attachment. An ultra-high-speed optical trap enabled direct observation of the timing and amplitude of the working stroke, which can occur within &...
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doaj-7e6497584f8c4b5f9f10fe21aaa0176a2021-05-05T17:55:36ZengeLife Sciences Publications LtdeLife2050-084X2019-09-01810.7554/eLife.49266Single molecule mechanics resolves the earliest events in force generation by cardiac myosinMichael S Woody0https://orcid.org/0000-0002-8292-2695Donald A Winkelmann1Marco Capitanio2E Michael Ostap3Yale E Goldman4https://orcid.org/0000-0002-2492-9194Graduate Group in Biochemistry and Molecular Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United StatesDepartment of Pathology and Laboratory Medicine, Robert Wood Johnson Medical School, Rutgers University, Piscataway, United StatesLENS - European Laboratory for Non-linear Spectroscopy, Sesto Fiorentino, Italy; Department of Physics and Astronomy, University of Florence, Sesto Fiorentino, ItalyPennsylvania Muscle Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United StatesPennsylvania Muscle Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United StatesKey steps of cardiac mechanochemistry, including the force-generating working stroke and the release of phosphate (Pi), occur rapidly after myosin-actin attachment. An ultra-high-speed optical trap enabled direct observation of the timing and amplitude of the working stroke, which can occur within <200 μs of actin binding by β-cardiac myosin. The initial actomyosin state can sustain loads of at least 4.5 pN and proceeds directly to the stroke or detaches before releasing ATP hydrolysis products. The rates of these processes depend on the force. The time between binding and stroke is unaffected by 10 mM Pi which, along with other findings, indicates the stroke precedes phosphate release. After Pi release, Pi can rebind enabling reversal of the working stroke. Detecting these rapid events under physiological loads provides definitive indication of the dynamics by which actomyosin converts biochemical energy into mechanical work.https://elifesciences.org/articles/49266myosinoptical trapcardiac myosinphosphate releaseworking strokestrong binding |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Michael S Woody Donald A Winkelmann Marco Capitanio E Michael Ostap Yale E Goldman |
spellingShingle |
Michael S Woody Donald A Winkelmann Marco Capitanio E Michael Ostap Yale E Goldman Single molecule mechanics resolves the earliest events in force generation by cardiac myosin eLife myosin optical trap cardiac myosin phosphate release working stroke strong binding |
author_facet |
Michael S Woody Donald A Winkelmann Marco Capitanio E Michael Ostap Yale E Goldman |
author_sort |
Michael S Woody |
title |
Single molecule mechanics resolves the earliest events in force generation by cardiac myosin |
title_short |
Single molecule mechanics resolves the earliest events in force generation by cardiac myosin |
title_full |
Single molecule mechanics resolves the earliest events in force generation by cardiac myosin |
title_fullStr |
Single molecule mechanics resolves the earliest events in force generation by cardiac myosin |
title_full_unstemmed |
Single molecule mechanics resolves the earliest events in force generation by cardiac myosin |
title_sort |
single molecule mechanics resolves the earliest events in force generation by cardiac myosin |
publisher |
eLife Sciences Publications Ltd |
series |
eLife |
issn |
2050-084X |
publishDate |
2019-09-01 |
description |
Key steps of cardiac mechanochemistry, including the force-generating working stroke and the release of phosphate (Pi), occur rapidly after myosin-actin attachment. An ultra-high-speed optical trap enabled direct observation of the timing and amplitude of the working stroke, which can occur within <200 μs of actin binding by β-cardiac myosin. The initial actomyosin state can sustain loads of at least 4.5 pN and proceeds directly to the stroke or detaches before releasing ATP hydrolysis products. The rates of these processes depend on the force. The time between binding and stroke is unaffected by 10 mM Pi which, along with other findings, indicates the stroke precedes phosphate release. After Pi release, Pi can rebind enabling reversal of the working stroke. Detecting these rapid events under physiological loads provides definitive indication of the dynamics by which actomyosin converts biochemical energy into mechanical work. |
topic |
myosin optical trap cardiac myosin phosphate release working stroke strong binding |
url |
https://elifesciences.org/articles/49266 |
work_keys_str_mv |
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