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#force

15 posts9 participants1 post today
Public
Rxiv mechanobio

📰 "Proteolytically activated antibacterial toxins inhibit the growth of diverse Gram-positive bacteria"
biorxiv.org/content/10.1101/20 #Force #Cell

bioRxiv · Proteolytically activated antibacterial toxins inhibit the growth of diverse Gram-positive bacteriaMany species of bacteria produce small-molecule antibiotics that enter and kill a wide range of competitor microbes. However, diffusible antibacterial proteins that share this broad-spectrum activity are not known to exist. Here, we report a family of proteins widespread in Gram-positive bacteria that display potent antibacterial activity against a diverse range of target organisms. Upon entering susceptible cells, these antibacterial proteins (ABPs) enzymatically degrade essential cellular components including DNA, tRNA, and rRNA. Unlike previously characterized bactericidal proteins, which require a specific cell surface receptor and therefore display a narrow spectrum of activity, we find that ABPs act in a receptor-independent manner and consequently kill bacteria spanning multiple bacterial phyla. Target cell entry by ABPs requires proteolytic activation by a cognate, co-exported serine protease and the liberated toxin component of the cleaved ABP is driven across the target cell membrane by the proton motive force. By examining representative ABPs from diverse pathogenic, commensal, and environmental bacteria, we show that broad-spectrum antibacterial activity is a conserved property of this protein family. Collectively, our work demonstrates that secreted proteins can act as broad-spectrum antibiotics, suggesting that ABPs represent one of potentially many such families produced in nature. ### Competing Interest Statement The authors have declared no competing interest.
Public
Rxiv mechanobio

📰 "Data-driven performance optimization of gamma spectrometers with many channels"
arxiv.org/abs/2504.07166 #Physics.Ins-Det #Matrix #Force

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arXiv.orgData-driven performance optimization of gamma spectrometers with many channelsIn gamma spectrometers with variable spectroscopic performance across many channels (e.g., many pixels or voxels), a tradeoff exists between including data from successively worse-performing readout channels and increasing efficiency. Brute-force calculation of the optimal set of included channels is exponentially infeasible as the number of channels grows, and approximate methods are required. In this work, we present a data-driven framework for attempting to find near-optimal sets of included detector channels. The framework leverages non-negative matrix factorization (NMF) to learn the behavior of gamma spectra across the detector, and clusters similarly-performing detector channels together. Performance comparisons are then made between spectra with channel clusters removed, which is more feasible than brute force. The framework is general and can be applied to arbitrary, user-defined performance metrics depending on the application. We apply this framework to optimizing gamma spectra measured by H3D M400 CdZnTe spectrometers, which exhibit variable performance across their crystal volumes. In particular, we show several examples optimizing various performance metrics for uranium and plutonium gamma spectra in nondestructive assay for nuclear safeguards, and explore trends in performance vs.\ parameters such as clustering algorithm type. We also compare the NMF+clustering pipeline to several non-machine-learning algorithms, including several greedy algorithms. Overall, we find that the NMF+clustering pipeline tends to find the best-performing set of detector voxels, significantly improving over the un-optimized spectra, but that a greedy accumulation of spectra segmented by detector depth can in some cases give similar performance improvements in much less computation time.
Public
Rxiv mechanobio

📰 "Feedback controlled microengine powered by motor protein"
arxiv.org/abs/2503.07112 #Cond-Mat.Mes-Hall #Physics.Bio-Ph #Microtubule #Force

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arXiv.orgFeedback controlled microengine powered by motor proteinWe present a template for realization of a novel microengine which is able to harness and convert the activity driven movement of individual motor protein into work output of the system. This engine comprises of a micron size bead-motor protein complex that is subject to a time-varying, feedback controlled optical potential, and a driving force due to the action of the motor protein which stochastically binds, walks and unbinds to an underlying microtubule filament. Using a Stochastic thermodynamics framework and theoretical modeling of bead-motor transport in a harmonic optical trap potential, we obtain the engine characteristics, e.g., work output per cycle, power generated, efficiency and the probability distribution function of the work output as a function of motor parameters and optical trap stiffness. The proposed engine is a work-to-work converter. Remarkably, the performance of this engine can vastly supersede the performance of other microengines that have been realized so far for feasible biological parameter range for kinesin-1 and kinesin-3 motor proteins. In particular, the work output per cycle is ~ (10-15) k_b T while the power output is (5-8) k_b T s^{-1}. Furthermore, we find that even with time delay in feedback protocol, the performance of the engine remains robust as long as the delay time is much smaller than the Brownian relaxation time of the micron size bead. Indeed such low delay time in feedback in the optical trap setup can easily be achieved with current Infrared (IR) lasers and optical trap sensor. The average work output and power output of the engine, exhibits interesting non-monotonic dependence on motor velocity and optical trap stiffness. As such this motor protein driven microengine can be a promising potential prototype for fabricating an actual microdevice engine which can have practical utility.
Public
Rxiv mechanobio

📰 "Characterization of a Novel FKS1 Mutation in Candida lusitaniae Shows a Potential Critical Role for MKC1 in Echinocandin Resistance"
biorxiv.org/content/10.1101/20 #Force #Cell

bioRxiv · Characterization of a Novel FKS1 Mutation in Candida lusitaniae Shows a Potential Critical Role for MKC1 in Echinocandin ResistanceCaspofungin is an echinocandin antifungal that inhibits glucan synthesis in the fungal cell wall. A Candida parapsilosis bloodstream isolate resistant to echinocandins was recovered from a patient who had undergone allogeneic hematopoietic stem cell transplantation. The FKS1 gene, encoding the target glucan synthase, contained a heterozygous mutation resulting in an I1380T amino acid change, in addition to the naturally occurring P660A polymorphism. When expressed at the equivalent position in the Fks1p protein of C. lusitaniae, P642A and I1359T, alone and in combination, led to 6-, 12-, and ≥256-fold increases in the minimal inhibitory concentration (MIC) of caspofungin, respectively. The caspofungin concentration needed to inhibit 50% of glucan synthase activity was increased 3-, 37-, and 270-fold, respectively. At high drug concentrations, and also in drug-free medium, infrared spectroscopy revealed a decrease in β-glucan content and an increase in chitin in the cell wall of the I1359T Fks1p mutants. Atomic force microscopy showed cell wall damage and cell swelling in both susceptible and resistant strains under caspofungin exposure. Analysis of susceptibility to cell-wall stressors and key factors in cell wall integrity (CWI) and high-osmolarity glycerol (HOG) pathways showed that all strains activated these pathways under caspofungin stress. In the I1359T Fks1p mutants, Mkc1p was constitutively activated even without caspofungin. Deletion of MKC1 restored caspofungin susceptibility, indicating that activation of the CWI pathway is a key molecular determinant of resistance in vitro to caspofungin in these mutants.
Public
Rxiv mechanobio

📰 "Force-insensitive myosin-I enhances endocytosis robustness through actin network-scale collective ratcheting"
biorxiv.org/content/10.1101/20 #Myosin #Force #Cell

bioRxiv · Force-insensitive myosin-I enhances endocytosis robustness through actin network-scale collective ratchetingForce production by Type-I myosins influences endocytic progression in many cell types. Since different myosin-I isoforms exhibit distinct force-dependent kinetic properties, it is important to investigate how these properties affect endocytic outcomes, and the mechanisms through which myosin-I contributes to endocytosis. To this end, we adapted our agent-based simulations of endocytic actin networks and incorporated nonprocessive, single-headed myosin motors at the base of the endocytic pit. We varied the unbinding rate and the force dependence of myosin unbinding. Our results revealed that the inclusion of myosin motors facilitated endocytic internalization, but only under kinetic regimes with rapid and less force-sensitive unbinding. Conversely, slow or strongly force-dependent unbinding impeded endocytic progression. As membrane tension increased, the boundary between assistive and inhibitory phases shifted, allowing the myosins to assist over larger regions of the kinetic landscape. Myosin-I's contribution to internalization could not be explained by direct force transduction or increased actin assembly. Instead, the myosins collectively bolstered the robustness of internalization by limiting pit retraction. ### Competing Interest Statement The authors have declared no competing interest.
Public
Rxiv mechanobio

📰 "Fully three-dimensional force inference in intestinal organoids reveals ratchet-like bud stabilization"
biorxiv.org/content/10.1101/20 #Mechanical #Force #Cell

bioRxiv · Fully three-dimensional force inference in intestinal organoids reveals ratchet-like bud stabilizationThe intestinal epithelium in vertebrates has a characteristic architecture of protruding villi and receding crypts that enables nutrient absorption and cellular turnover. Intestinal organoids recapitulate its development and can be used as disease models, but the underlying mechanical processes are not fully understood yet. Here we combine advanced image processing and the bubbly vertex model for epithelial cell shape to achieve a fully three-dimensional reconstruction of cell shapes and forces during the development of mouse intestinal organoids. We show that the transition to budded morphologies is caused by a global increase in apical tension, which however is not maintained after budding, suggesting ratchet-like non-reversibility. We further demonstrate that luminal pressure decreases and basal line tensions increase during development, thus facilitating budding on the apical side, but at the same time mechanically stabilizing the system at the basal side, for example against cell extrusion. Our approach demonstrates how one can achieve a complete mechanical analysis of a complex tissue-like system. ### Competing Interest Statement The authors have declared no competing interest.
Public
Rxiv mechanobio

📰 "Enterovirus D68 infection of human inducible pluripotent stem cell-derived skeletal muscles resulted in structural destruction, loss of muscle function and hampered muscle regeneration"
biorxiv.org/content/10.1101/20 #Force #Cell

bioRxiv · Enterovirus D68 infection of human inducible pluripotent stem cell-derived skeletal muscles resulted in structural destruction, loss of muscle function and hampered muscle regenerationEnterovirus D68 (EV-D68) is an emerging respiratory virus that commonly causes mild to severe respiratory diseases. EV-D68 infection is also associated with extra-respiratory complications, especially acute flaccid myelitis. However, how the virus invades the central nervous system (CNS) and infects motor neurons is not fully understood. One possible neuroinvasive route is through infection of skeletal muscles, which allows the virus to infect motor neurons via the neuromuscular junction. However, we hypothesise that direct EV-D68 infection of human skeletal muscles can impair muscle function and thus contribute to the development of EV-D68-associated muscle weakness. Here, we inoculated human induced pluripotent stem cell-derived skeletal muscle myotubes grown in 2D with different EV-D68 isolates, which resulted in a productive infection and cell death. We showed, through neuraminidase treatment, that sialic acids facilitate infection of these cells. EV-D68 infection of 3D tissue engineered skeletal muscles led to tissue damage, reduction of contractile force and depletion of muscle and satellite cells. Altogether, we showed that human skeletal muscle can act as an extra-respiratory replication site and infection of skeletal muscles may contribute to EV-D68-associated muscle weakness. ### Competing Interest Statement The authors have declared no competing interest.
Public
Rxiv mechanobio

📰 "Morphological Effects on Bacterial Brownian Motion: Validation of a Chiral Two-Body Model"
arxiv.org/abs/2504.05053 #Physics.Flu-Dyn #Force #Cell

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arXiv.orgMorphological Effects on Bacterial Brownian Motion: Validation of a Chiral Two-Body ModelDuring bacterial swimming, thermal noise inevitably affects their motion, while the flagellum not only propels the bacteria, but also plays a crucial role in enhancing the stability of their forward direction. In this study, we aim to validate the effectiveness of a previously established chiral two-body model for simulating bacterial Brownian motion, which simplifies the helical flagellum to a chiral body. We systematically investigate bacterial motion using the chiral two-body model, resistive force theory, and twin multipole moment. We validate the effectiveness of the model by comparing the standard deviations of the flagellar random velocities obtained from different methods. The analytical solutions for the velocities, the thrust, and torque exerted by the motor on the cell body are derived from the chiral two-body model during bacterial non-Brownian motion. We characterize the shape and symmetry of the trajectories through the eigenvalues of the radius of gyration tensor, describe their linearity employing the directionality ratio, and evaluate the stability of forward direction using the average orientation. We conclude that appropriately increasing the helix radius and the contour length of the flagellum can elongate trajectories and enhance linearity. In addition, the longer contour length increases the average orientation, thereby enhancing the stability of the bacterial forward direction. This study further validates the effectiveness of the chiral two-body model in simulating bacterial Brownian motion and indicates the importance of the flagellum in stabilizing bacterial Brownian motion.
Public
Ari 🏳️‍⚧️

There are only four fundamental forces in nature-
1. Gravitational Force - Acts between objects with mass.
2. Electromagnetic Force - Acts between objects with charge.
3. Weak Nuclear Force - Acts during beta decay.
4. Strong Nuclear Forces - Acts between nucleons(protons and neutrons) when seperation between them is less than 10^-15 m.

#physics#force
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