# CHEMOMECHANICAL PROCESSES IN CROSS-BRIDGE KINETICS

> **NIH NIH R01** · UNIVERSITY OF IOWA · 1990 · $137,633

## Abstract

The molecular mechanisms of contraction is probed in a skinned fiber
system, in which the lattice spacing of the thick and thin filaments is
osmotically altered.  The length of an active muscle fiber is changed
sinusoidally or in a stepwise fashion, and a concomitant tension time
course is analyzed in terms of exponential rate constants.  Two hypotheses
predicting the effect of the lattice spacing on the crossbridge kinetics
are tested.  These include: (i) a reduction of the rate constant of
actomyosin dissociation at a low level of compression, and (ii) a reduction
of the rate constant of the power stroke at a high level of compression.
Both the rate constants of the MgATP binding to actomyosin and of the
dissociation which ensues the binding can be obtained by studying the MgATP
dependence of the exponential rate constants.  Th rate constant(s) which
involves the power stroke reaction(s) can be obtained by studying the Ca
effect.  The equilibrium constant between the detached stae and the
pre-tension state is estimated, based on the ionic strength effect on
tension, stiffness, and the rate constants.  We will then change the
sarcomere length, and study the rate constants to determine whether the
results can be predicted based on the change in the lattice spacing.  The
sarcomere length study will also be carried out on intact preparations
where the quality of the data is better, although the solution parameters
cannot be controlled as in skinned fibers.  In other series of experiments,
the lattice spacing is measured by low angle equitorial X-ray diffraction
studies, and their results are correlated with the crossbridge kinetics.
In skinned fibers, the ATPase rate is measured to examine if the rate
limiting step is influenced by the lattice spacing change.  Nonlinear
profiles of the exponential rate constants are measured primarily in the
step analysis method.  All of these results are used to construct a
crossbridge model, which will account for the Ca and MgATP effects on the
exponential rate constants, as well as the effect of the lattice spacing
and the ionic strength.  The knowledge acquire and the technique developed
during the course of this research can ultimately be applied to the study
of muscle dysfunction.

## Key facts

- **NIH application ID:** 3155181
- **Project number:** 5R01AR021530-11
- **Recipient organization:** UNIVERSITY OF IOWA
- **SAM.gov UEI:** Z1H9VJS8NG16
- **Principal Investigator:** MASATAKA KAWAI
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1990
- **Award amount:** $137,633
- **Award type:** 5
- **Project period:** 1987-07-01 → 1992-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3155181

## Citation

> US National Institutes of Health, RePORTER application 3155181, CHEMOMECHANICAL PROCESSES IN CROSS-BRIDGE KINETICS (5R01AR021530-11). Retrieved via MORVS 2026-10-24 from https://api.morvs.ai/grant/nih/3155181. Licensed CC0.

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