Robust mechanobiological behavior emerges in heterogeneous myosin systems

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.

Modeling mechanochemical pattern formation in elastic sheets of biological matter

“…Physically speaking, chemical or motor fraction rearrangements evolve on longer time scales, whereas fast modes of mechanical conformations follow them quasi-statically. For an epithelial monolayer, we estimate a characteristic timescale of ∼ 10 1 -10 2 s for relaxation of elastic deformation energy [21,31], while morphogen degradation occurs over tens of minutes to hours [50,51]. A similar comparison of timescales can be made for the cell cytoskeleton or actin-myosin gels in vitro that are simulated in Model II.…”

“…Here we explore the dynamics and pattern formation in a contractile sheet in the regime when feedback between the developed tension and motor unbinding rate is strong. The characteristic detachment rate is chosen to be much larger than the binding rate ( koff = 10, k on = 0.2) [51]. Thus, without feedback, the bound motor fraction, m, decreases fast, approaching a steady state value.…”

Functionality of Disorder in Muscle Mechanics

“…The idea that actomyosin disregistry brings the system's stiffness to zero was pioneered in [26]. More recently the utility of quenched disorder for the active aspects of muscle mechanics has been advocated in [27]. The beneficial role of random inhomogeneity has been established in many other fields of physics from hightemperature superconductivity in electronic materials [28] to Griffiths phases in brain networks [29].…”

Storytelling as a Tool to Enhance Conceptual Knowledge in Cell Biology

“…For these students, understanding the connection to applications is a strong driver that could be used to motivate much of the content. One of the most difficult aspects of cell biology education is integrating multiple levels of information into a coherent picture that highlights biomedical applications for which cell biology is an essential tool, such as cell fate, disease pathogenesis, and drug effects ( 4 , 5 ). The second big challenge is demonstrating that the material described in class is relevant ( 6 ).…”