The Molecular Mechanics of Muscle
: Discrete modelling of myosin motors demonstrates cooperative and synchronistic behaviours

Student thesis: Doctoral ThesisDoctor of Philosophy (PhD)

Abstract

Groups of non-processive myosin motors exhibit complex behaviors when interacting with actin filaments, often operating at larger scales and time frames than individual myosin heads. This suggests strong cooperative dynamics, but the underlying interactions driving this emergent behavior remain unclear. Here we demonstrate the diversity of in vitro behaviours can be captured by a simple mechanical model based off a network of phase oscillators. The model mirrors the inverse hyperbolic force-velocity curve and linear force-motor fraction relations typical of actomyosin systems, as well as the spontaneous saw-tooth oscillations present in in vitro actomyosin experiments. This suggests actomyosin-like behavior arises as a property of the discontinuous coupling in an incommensurate architecture, rather than specific to molecular motor reaction kinetics. A lack of dependence on motor-specific qualities to achieve function implies non-biological motors can cooperate similarly to biological motors when within an actomyosin geometry.
We stretch this concept to the architecture of a sarcomere, allowing us to interrogate how the specific regular blunted sawtooth form of sarcomeric spontaneous oscillatory contractions occurs, wherein individual filaments enter an unbinding/binding cycle at the cusp of the oscillation before releasing. Using insights gained from the internal dynamics shown by this model we propose a third stage to the as of yet two stage oscillation cycle.
Finally we build a chemo-mechanical model, involving both complex binding kinetics and a non-linear mechanical environment. We show that, despite its complexity the results achieved are quite similar to our minimal rotor model, adding further veracity to our initial abstractions.
Ultimately, we present a versatile and scalable modelling framework for molecular motor systems, demonstrating its alignment with experimental data and potential applicability to non-biological motors, particularly in in emulating actomyosin-like behaviors within contemporary robotics.
Date of Award4 Feb 2025
Original languageEnglish
Awarding Institution
  • University of Bristol
SupervisorHermes Gadelha (Supervisor) & Jonathan M Rossiter (Supervisor)

Keywords

  • Myosin
  • Molecular motors
  • Molecular biology
  • Synchronisation
  • Mechanical parallel
  • Computational biology
  • Mathematical biology

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