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

arXiv logo
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.

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

arXiv logo
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.

📰 "Whole-cell particle-based digital twin simulations from 4D lattice light-sheet microscopy data"
biorxiv.org/content/10.1101/20
#Microtubule

bioRxiv · Whole-cell particle-based digital twin simulations from 4D lattice light-sheet microscopy dataWe present a framework for performing whole-cell digital twin simulations which integrates 4D (x,y,z,t) lattice light-sheet microscopy (LLSM) data with particle-based reaction-diffusion modeling to capture intracellular organelle dynamics. Using imaging data from Cal27 cells, we construct digital twins that incorporate mitochondrial networks, microtubule networks, dynein and kinesin motors, the plasma membrane, and the nucleus. Passive diffusive mitochondrial dynamics are parameterized using stochastic reaction-diffusion simulations in ReaDDy, while active transport is modeled explicitly by incorporating motor-driven transport along a diffusing, polarized microtubule network. Our simulations accurately reproduce experimentally observed mitochondrial dynamics across pharmacological microtubule depolymerization conditions and reproduce the mitochondrial response to intermediate perturbations without explicit re-parameterization. This novel meso-scale digital twin framework offers a bridge between atomic-scale whole-cell simulations and experimental time and length scales. ### Competing Interest Statement The authors have declared no competing interest.

📰 "Profiling the gut and oral microbiota of hormone receptor-positive, HER2-negative metastatic breast cancer patients receiving pembrolizumab and eribulin"
doi.org/doi:10.20517/mrr.2024.
pubmed.ncbi.nlm.nih.gov/402072
#Microtubule

Microbiome Research ReportsProfiling the gut and oral microbiota of hormone receptor-positive, HER2-negative metastatic breast cancer patients receiving pembrolizumab and eribulinAim: Changes in host-associated microbial communities (i.e., the microbiota) may modulate responses to checkpoint blockade immunotherapy. In the KELLY phase II study (NCT03222856), we previously demonstrated that pembrolizumab [anti-programmed cell death protein 1 (PD-1)] combined with eribulin (plus microtubule-targeting chemotherapy) showed encouraging antitumor activity in patients with hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (mBC) who had received prior treatments.Methods: A total of 58 fecal and 67 saliva samples were prospectively collected from a subset of 28 patients at baseline (BL), after three treatment cycles, and end of treatment. Shotgun metagenomics, 16S rRNA gene amplicon sequencing, and bioinformatics and statistical approaches were used to characterize fecal and oral microbiota profiles.Results: Treatment caused no substantial perturbations in gut or oral microbiota, suggesting minimal drug-related microbial toxicity. Bacteroides and Faecalibacterium were the dominant gut microbiota genera, while Prevotella and Streptococcus were present in both oral and gut samples, highlighting potential gut-oral microbial interactions. Additionally, clinical benefit (CB) appeared to be associated with gut-associated Bacteroides fragilis (B. fragilis) and a BL oral abundance of Streptococcus ≥ 30%. Notably, B. fragilis NCTC 9343 supernatant induced dose-dependent lactate dehydrogenase (LDH) release from the MCF-7 (HR-positive/HER2-negative) BC cell line.Conclusion: These findings suggest that specific gut and oral microbiota may modulate the effectiveness of combinatory anti-BC therapies, potentially through the action of microbial metabolites.

📰 "Glial betaPix is essential for blood vessel integrity in the zebrafish brain"
biorxiv.org/content/10.1101/20
#Microtubule

bioRxiv · Glial betaPix is essential for blood vessel integrity in the zebrafish brainThe formation of blood-brain barrier and vascular integrity depends on the coordinative development of different cell types in the brain. Previous studies have shown that zebrafish bubblehead mutant, which has mutation in the betaPix locus, develops spontaneous intracerebral hemorrhage during early development. However, it remains unclear in which brain cells betaPix may function. Here, we established a highly efficient conditional knockout method in zebrafish by using homology-directed repair (HDR)-mediated knockin and knockout technology, and generated betaPix conditional trap ( betaPixct ) allele in zebrafish. We found that betaPix in glia, but neither neurons, endothelial cells, nor pericytes, was critical for glial and vascular development and integrity, thus contributing to the formation of blood-brain barrier. Single-cell transcriptome profiling revealed that microtubule aggregation signaling stathmins and pro-angiogenic transcription factors Zfhx3/4 were down-regulated in glial and neuronal progenitors, and further genetic analysis suggested that betaPix acted upstream on the PAK1-Stathmin and Zfhx3/4-Vegfaa signaling to regulate glia migration and vascular integrity. Therefore, this work reveals that glial betaPix plays an important role in brain vascular integrity in zebrafish embryos and possibly human cells. ### Competing Interest Statement The authors have declared no competing interest.