The mechano-chemistry of cytoskeletal force generation

In this communication, we propose a model to study the non-equilibrium process by which actin stress fibers develop force in contractile cells. The emphasis here is on the non-equilibrium thermodynamics, which is necessary to address the mechanics as well as the chemistry of dynamic cell contractility. In this setting we are able to develop a framework that relates (a) the dynamics of force generation within the cell and (b) the cell response to external stimuli to the chemical processes occurring within the cell, as well as to the mechanics of linkage between the stress fibers, focal adhesions and extra-cellular matrix.Comment: 22 pages, 6 figures, 1 table, accepted in Biomechanics and Modeling in Mechanobiolog

Emergence of electromotive force in precession-less rigid motion of deformed domain wall

Recently it has been recognized that the electromotive force (emf) can be induced just by the spin precession where the generation of the electromotive force has been considered as a real-space topological pumping effect. It has been shown that the amount of the electromotive force is independent of the functionality of the localized moments. It was also demonstrated that the rigid domain wall (DW) motion cannot generate electromotive force in the system. Based on real-space topological pumping approach in the current study we show that the electromotive force can be induced by rigid motion of a deformed DW. We also demonstrate that the generated electromotive force strongly depends on the DW bulging. Meanwhile results show that the DW bulging leads to generation of the electromotive force both along the axis of the DW motion and normal to the direction of motion

Microstructural analysis of skeletal muscle force generation during aging.

Human aging results in a progressive decline in the active force generation capability of skeletal muscle. While many factors related to the changes of morphological and structural properties in muscle fibers and the extracellular matrix (ECM) have been considered as possible reasons for causing age-related force reduction, it is still not fully understood why the decrease in force generation under eccentric contraction (lengthening) is much less than that under concentric contraction (shortening). Biomechanically, it was observed that connective tissues (endomysium) stiffen as ages, and the volume ratio of connective tissues exhibits an age-related increase. However, limited skeletal muscle models take into account the microstructural characteristics as well as the volume fraction of tissue material. This study aims to provide a numerical investigation in which the muscle fibers and the ECM are explicitly represented to allow quantitative assessment of the age-related force reduction mechanism. To this end, a fiber-level honeycomb-like microstructure is constructed and modeled by a pixel-based Reproducing Kernel Particle Method (RKPM), which allows modeling of smooth transition in biomaterial properties across material interfaces. The numerical investigation reveals that the increased stiffness of the passive materials of muscle tissue reduces the force generation capability under concentric contraction while maintains the force generation capability under eccentric contraction. The proposed RKPM microscopic model provides effective means for the cellular-scale numerical investigation of skeletal muscle physiology. NOVELTY STATEMENT: A cellular-scale honeycomb-like microstructural muscle model constructed from a histological cross-sectional image of muscle is employed to study the causal relations between age-associated microstructural changes and age-related force loss using Reproducing Kernel Particle Method (RKPM). The employed RKPM offers an effective means for modeling biological materials based on pixel points in the medical images and allow modeling of smooth transition in the material properties across interfaces. The proposed microstructure-informed muscle model enables quantitative evaluation on how cellular-scale compositions contribute to muscle functionality and explain differences in age-related force changes during concentric, isometric and eccentric contractions

The wake dynamics and flight forces of the fruit fly Drosophila melanogaster

We have used flow visualizations and instantaneous force measurements of tethered fruit flies (Drosophila melanogaster) to study the dynamics of force generation during flight. During each complete stroke cycle, the flies generate one single vortex loop consisting of vorticity shed during the downstroke and ventral flip. This gross pattern of wake structure in Drosophila is similar to those described for hovering birds and some other insects. The wake structure differed from those previously described, however, in that the vortex filaments shed during ventral stroke reversal did not fuse to complete a circular ring, but rather attached temporarily to the body to complete an inverted heart-shaped vortex loop. The attached ventral filaments of the loop subsequently slide along the length of the body and eventually fuse at the tip of the abdomen. We found no evidence for the shedding of wing-tip vorticity during the upstroke, and argue that this is due to an extreme form of the Wagner effect acting at that time. The flow visualizations predicted that maximum flight forces would be generated during the downstroke and ventral reversal, with little or no force generated during the upstroke. The instantaneous force measurements using laser-interferometry verified the periodic nature of force generation. Within each stroke cycle, there was one plateau of high force generation followed by a period of low force, which roughly correlated with the upstroke and downstroke periods. However, the fluctuations in force lagged behind their expected occurrence within the wing-stroke cycle by approximately 1 ms or one-fifth of the complete stroke cycle. This temporal discrepancy exceeds the range of expected inaccuracies and artifacts in the measurements, and we tentatively discuss the potential retarding effects within the underlying fluid mechanics

Neck linker docking is critical for Kinesin-1 force generation in cells but at a cost to motor speed and processivity.

Kinesin force generation involves ATP-induced docking of the neck linker (NL) along the motor core. However, the roles of the proposed steps of NL docking, cover-neck bundle (CNB) and asparagine latch (N-latch) formation, during force generation are unclear. Furthermore, the necessity of NL docking for transport of membrane-bound cargo in cells has not been tested. We generated kinesin-1 motors impaired in CNB and/or N-latch formation based on molecular dynamics simulations. The mutant motors displayed reduced force output and inability to stall in optical trap assays but exhibited increased speeds, run lengths, and landing rates under unloaded conditions. NL docking thus enhances force production but at a cost to speed and processivity. In cells, teams of mutant motors were hindered in their ability to drive transport of Golgi elements (high-load cargo) but not peroxisomes (low-load cargo). These results demonstrate that the NL serves as a mechanical element for kinesin-1 transport under physiological conditions