Robust mechanobiological behavior emerges in heterogeneous myosin systems

Paul F. Egan, Jeffrey R. Moore, Allen J. Ehrlicher, David A. Weitz, Christian Schunn, Jonathan Cagan, Philip LeDuc

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

Biological complexity presents challenges for understanding natural phenomenon and engineering new technologies, particularly in systems with molecular heterogeneity. Such complexity is present in myosin motor protein systems, and computational modeling is essential for determining how collective myosin interactions produce emergent system behavior. We develop a computational approach for altering myosin isoform parameters and their collective organization, and support predictions with in vitro experiments of motility assays with α-actinins as molecular force sensors. The computational approach models variations in single myosin molecular structure, system organization, and force stimuli to predict system behavior for filament velocity, energy consumption, and robustness. Robustness is the range of forces where a filament is expected to have continuous velocity and depends on used myosin system energy. Myosin systems are shown to have highly nonlinear behavior across force conditions that may be exploited at a systems level by combining slow and fast myosin isoforms heterogeneously. Results suggest some heterogeneous systems have lower energy use near stall conditions and greater energy consumption when unloaded, therefore promoting robustness. These heterogeneous system capabilities are unique in comparison with homogenous systems and potentially advantageous for high performance bionanotechnologies. Findings open doors at the intersections of mechanics and biology, particularly for understanding and treating myosin-related diseases and developing approaches for motor molecule-based technologies.

Original languageEnglish
Pages (from-to)E8147-E8154
JournalProceedings of the National Academy of Sciences of the United States of America
Volume114
Issue number39
DOIs
StatePublished - Sep 26 2017

Keywords

  • Biophysics
  • Complexity
  • Computational biology
  • Myosin
  • Robustness

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