Myosin and [Formula: see text]-actinin regulation of stress fiber contractility under tensile stress.

Stress fibers are actomyosin bundles that regulate cellular mechanosensation and force transduction. Interacting with the extracellular matrix through focal adhesion complexes, stress fibers are highly dynamic structures regulated by myosin motors and crosslinking proteins. Under external mechanical stimuli such as tensile forces, the stress fiber remodels its architecture to adapt to external cues, displaying properties of viscoelastic materials. How the structural remodeling of stress fibers is related to the generation of contractile force is not well understood. In this work, we simulate mechanochemical dynamics and force generation of stress fibers using the molecular simulation platform MEDYAN. We model stress fiber as two connecting bipolar bundles attached at the ends to focal adhesion complexes. The simulated stress fibers generate contractile force that is regulated by myosin motors and [Formula: see text]-actinin crosslinkers. We find that stress fibers enhance contractility by reducing the distance between actin filaments to increase crosslinker binding, and this structural remodeling ability depends on the crosslinker turnover rate. Under tensile pulling force, the stress fiber shows an instantaneous increase of the contractile forces followed by a slow relaxation into a new steady state. While the new steady state contractility after pulling depends only on the overlap between actin bundles, the short-term contractility enhancement is sensitive to the tensile pulling distance. We further show that this mechanical response is also sensitive to the crosslinker turnover rate. Our results provide new insights into the stress fiber mechanics that have significant implications for understanding cellular adaptation to mechanical signaling.

Effects of Acremonium cellulase and heat-resistant lactic acid bacteria on lignocellulose degradation, fermentation quality, and microbial community structure of hybrid elephant grass silage in humid and hot areas.

To better evaluate the effects of Acremonium cellulase (AC) and previously screened heat-resistant Lactobacillus plantarum 149 (LP149) on lignocellulose degradation, fermentation quality, and microbial community during ensiling in humid and hot areas, this study used a small-scale fermentation system to prepare hybrid elephant grass silage at 30 and 45°C, respectively. Compared to control and commercial inoculant Lactobacillus plantarum (LP), the addition of AC or strain LP149 decreased the contents of neutral detergent fiber, acid detergent fiber, and cellulose and increased the contents of glucose, fructose, and sucrose during fermentation. Furthermore, AC and LP149 treatments altered the microbial communities' structure during ensiling. AC treatment provided more substrate for microbial fermentation, resulting in an increase in bacterial alpha diversity. LP149 treatment increased the Lactobacillus abundance and optimized the bacterial community compositions. In addition, AC and LP149 treatments had higher (P < 0.05) lactic acid and acetic acid contents and lower (P < 0.05) pH, butyric acid, and NH3-N levels compared to the control. These results indicated that AC and strain LP149 are promising silage additives that can promote lignocellulose degradation and improve the fermentation quality of hybrid elephant grass in humid and hot areas.

A tug of war between filament treadmilling and myosin induced contractility generates actin rings.

In most eukaryotic cells, actin filaments assemble into a shell-like actin cortex under the plasma membrane, controlling cellular morphology, mechanics, and signaling. The actin cortex is highly polymorphic, adopting diverse forms such as the ring-like structures found in podosomes, axonal rings, and immune synapses. The biophysical principles that underlie the formation of actin rings and cortices remain unknown. Using a molecular simulation platform called MEDYAN, we discovered that varying the filament treadmilling rate and myosin concentration induces a finite size phase transition in actomyosin network structures. We found that actomyosin networks condense into clusters at low treadmilling rates or high myosin concentrations but form ring-like or cortex-like structures at high treadmilling rates and low myosin concentrations. This mechanism is supported by our corroborating experiments on live T cells, which exhibit ring-like actin networks upon activation by stimulatory antibody. Upon disruption of filament treadmilling or enhancement of myosin activity, the pre-existing actin rings are disrupted into actin clusters or collapse towards the network center respectively. Our analyses suggest that the ring-like actin structure is a preferred state of low mechanical energy, which is, importantly, only reachable at sufficiently high treadmilling rates.

On Stretching, Bending, Shearing, and Twisting of Actin Filaments I: Variational Models.

Mechanochemical simulations of actomyosin networks are traditionally based on one-dimensional models of actin filaments having zero width. Here, and in the follow up paper (arXiv, DOI 10.48550/arXiv.2203.01284), approaches are presented for more efficient modeling that incorporates stretching, shearing, and twisting of actin filaments. Our modeling of a semiflexible filament with a small but finite width is based on the Cosserat theory of elastic rods, which allows for six degrees of freedom at every point on the filament's backbone. In the variational models presented in this paper, a small and discrete set of parameters is used to describe a smooth filament shape having all degrees of freedom allowed in the Cosserat theory. Two main approaches are introduced: one where polynomial spline functions describe the filament's configuration, and one in which geodesic curves in the space of the configurational degrees of freedom are used. We find that in the latter representation the strain energy function can be calculated without resorting to a small-angle expansion, so it can describe arbitrarily large filament deformations without systematic error. These approaches are validated by a dynamical model of a Cosserat filament, which can be further extended by using multiresolution methods to allow more detailed monomer-based resolution in certain parts of the actin filament, as introduced in the follow up paper. The presented framework is illustrated by showing how torsional compliance in a finite-width filament can induce broken chiral symmetry in the structure of a cross-linked bundle.

Membrane-MEDYAN: Simulating Deformable Vesicles Containing Complex Cytoskeletal Networks.

The plasma membrane defines the shape of the cell and plays an indispensable role in bridging intra- and extracellular environments. Mechanochemical interactions between plasma membrane and cytoskeleton are vital for cell biomechanics and mechanosensing. A computational model that comprehensively captures the complex, cell-scale cytoskeleton-membrane dynamics is still lacking. In this work, we introduce a triangulated membrane model that accounts for the membrane's elastic properties, as well as for membrane-filament steric interactions. The corresponding force-field was incorporated into the active biological matter simulation platform, MEDYAN ("mechanochemical dynamics of active networks"). Simulations using the new model shed light on how actin filament bundling affects generation of tubular membrane protrusions. In particular, we used membrane-MEDYAN simulations to investigate protrusion initiation and dynamics while varying geometries of filament bundles, membrane rigidities and local G-Actin concentrations. We found that the bundles' protrusion propensities sensitively depend on the synergy between bundle thickness and inclination angle at which the bundle approaches the membrane. The new model paves the way for simulations of biological systems involving intricate membrane-cytoskeleton interactions, such as those occurring at the leading edge and the cortex, eventually helping to uncover the fundamental principles underlying the active matter organization in the vicinity of the membrane.