# Dual filament control of myocardial power and hemodynamics

> **NIH NIH R01** · UNIVERSITY OF MISSOURI-COLUMBIA · 2020 · $480,860

## Abstract

Abstract
The capacity of the ventricles to perform work (i.e., generate power) is essential for moving blood throughout
the circulatory systems. Ventricular power is determined by the power generating capacity of the myofilaments
within the cardiac myocyte. However, the sub-cellular processes that regulate myofilament power are
incompletely understood. The overall objective of this proposal is to use biochemical, biophysical, and
transgenic tools to discern (i) thin filament and (ii) thick filament-based mechanisms that regulate power and
(iii) integrate these control mechanisms into a computational model that can predict how sarcomere-level
modifications impact hemodynamics. The two mechanistic hypotheses are (Aim 1) alterations in the functional
rigidity of thin filament regulatory units modulate cooperative recruitment of cross-bridges, which, in turn,
determines power and (Aim 2) phosphorylation of myosin binding protein- C (MyBP-C) per se increases
myofibrillar power output by three distinct biophysical mechanisms. In (Aim 3), a multi-state kinetic model of
sarcomeric power output will be generated whereby thin and thick filament dynamic properties can be
manipulated and evaluated for functional impacts to cooperativity and power. Aim 3 goes beyond the
sarcomere and uses multiscale modeling to predict how strategic manipulation of myofilament targets will
impact ventricular function and hemodynamics, which will be experimentally tested in a hypothesis-driven
manner. Multi-scale modeling will provide a new platform to interrogate biophysical modifications that produce
the largest functional effects and, thus, illuminate high-value therapeutic targets to optimize ventricular
performance in patients with genetic and adaptive cardiomyopathies.

## Key facts

- **NIH application ID:** 10072444
- **Project number:** 1R01HL148785-01A1
- **Recipient organization:** UNIVERSITY OF MISSOURI-COLUMBIA
- **Principal Investigator:** Kenneth S Campbell
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $480,860
- **Award type:** 1
- **Project period:** 2020-08-25 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10072444

## Citation

> US National Institutes of Health, RePORTER application 10072444, Dual filament control of myocardial power and hemodynamics (1R01HL148785-01A1). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10072444. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*