Shu-Ang Li, Xiao-Yan Meng, Su Zhang, Ying-Jie Zhang, Run-Zhou Yang, Dian-Dian Wang, Yang Yang, Pei-Pei Liu, Jian-Sheng Kang
{"title":"A Unified Intracellular pH Landscape with SITE-pHorin: a Quantum-Entanglement-Enhanced pH Probe","authors":"Shu-Ang Li, Xiao-Yan Meng, Su Zhang, Ying-Jie Zhang, Run-Zhou Yang, Dian-Dian Wang, Yang Yang, Pei-Pei Liu, Jian-Sheng Kang","doi":"arxiv-2407.04232","DOIUrl":"https://doi.org/arxiv-2407.04232","url":null,"abstract":"An accurate map of intracellular organelle pH is crucial for comprehending\u0000cellular metabolism and organellar functions. However, a unified intracellular\u0000pH spectrum using a single probe is still lack. Here, we developed a novel\u0000quantum entanglement-enhanced pH-sensitive probe called SITE-pHorin, which\u0000featured a wide pH-sensitive range and ratiometric quantitative measurement\u0000capabilities. Subsequently, we measured the pH of various organelles and their\u0000sub-compartments, including mitochondrial sub-spaces, Golgi stacks, endoplasmic\u0000reticulum, lysosomes, peroxisomes, and endosomes in COS-7 cells. For the\u0000long-standing debate on mitochondrial compartments pH, we measured the pH of\u0000mitochondrial cristae as 6.60 pm 0.40, the pH of mitochondrial intermembrane\u0000space as 6.95 pm 0.30, and two populations of mitochondrial matrix pH at\u0000approximately 7.20 pm 0.27 and 7.50 pm 0.16, respectively. Notably, the\u0000lysosome pH exhibited a single, narrow Gaussian distribution centered at 4.79\u0000pm 0.17. Furthermore, quantum chemistry computations revealed that both the\u0000deprotonation of the residue Y182 and the discrete curvature of deformed\u0000benzene ring in chromophore are both necessary for the quantum entanglement\u0000mechanism of SITE-pHorin. Intriguingly, our findings reveal an accurate pH\u0000gradient (0.6-0.9 pH unit) between mitochondrial cristae and matrix, suggesting\u0000prior knowledge about Delta pH (0.4-0.6) and mitochondrial proton motive force\u0000(pmf) are underestimated.","PeriodicalId":501170,"journal":{"name":"arXiv - QuanBio - Subcellular Processes","volume":"38 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141573610","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Membrane-mediated interactions between arc-shaped particles strongly depend on membrane curvature","authors":"Francesco Bonazzi, Thomas R. Weikl","doi":"arxiv-2407.04027","DOIUrl":"https://doi.org/arxiv-2407.04027","url":null,"abstract":"Besides direct molecular interactions, proteins and nanoparticles embedded in\u0000or adsorbed to membranes experience indirect interactions that are mediated by\u0000the membranes. These membrane-mediated interactions arise from the membrane\u0000curvature induced by the particles and can lead to assemblies of particles that\u0000generate highly curved spherical or tubular membranes shapes, but have mainly\u0000been quantified for planar or weakly curved membranes. In this article, we\u0000systematically investigate the membrane-mediated interactions of arc-shaped\u0000particles adsorbed to a variety of tubular and spherical membrane shapes with\u0000coarse-grained modelling and simulations. We determine both the pairwise\u0000interaction free energy, with includes entropic contributions due to rotational\u0000entropy loss at close particle distances, and the pairwise interaction energy\u0000without entropic components from particle distributions observed in the\u0000simulations. For membrane shapes with small curvature, the membrane-mediated\u0000interaction free energies of particle pairs exceed the thermal energy kT and\u0000can lead to particle ordering and aggregation. The interactions strongly\u0000decrease with increasing curvature of the membrane shape and are minimal for\u0000tubular shapes with membrane curvatures close to the particle curvature.","PeriodicalId":501170,"journal":{"name":"arXiv - QuanBio - Subcellular Processes","volume":"28 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141573611","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Efficient approximations of transcriptional bursting effects on the dynamics of a gene regulatory network","authors":"Jochen Kursawe, Antoine Moneyron, Tobias Galla","doi":"arxiv-2406.19109","DOIUrl":"https://doi.org/arxiv-2406.19109","url":null,"abstract":"Mathematical models of gene regulatory networks are widely used to study cell\u0000fate changes and transcriptional regulation. When designing such models, it is\u0000important to accurately account for sources of stochasticity. However, doing so\u0000can be computationally expensive and analytically untractable, posing limits on\u0000the extent of our explorations and on parameter inference. Here, we explore\u0000this challenge using the example of a simple auto-negative feedback motif, in\u0000which we incorporate stochastic variation due to transcriptional bursting and\u0000noise from finite copy numbers. We find that transcriptional bursting may\u0000change the qualitative dynamics of the system by inducing oscillations when\u0000they would not otherwise be present, or by magnifying existing oscillations. We\u0000describe multiple levels of approximation for the model in the form of\u0000differential equations, piecewise deterministic processes, and stochastic\u0000differential equations. Importantly, we derive how the classical chemical\u0000Langevin equation can be extended to include a noise term representing\u0000transcriptional bursting. This approximation drastically decreases computation\u0000times and allows us to analytically calculate properties of the dynamics, such\u0000as their power spectrum. We explore when these approximations break down and\u0000provide recommendations for their use. Our analysis illustrates the importance\u0000of accounting for transcriptional bursting when simulating gene regulatory\u0000network dynamics and provides recommendations to do so with computationally\u0000efficient methods.","PeriodicalId":501170,"journal":{"name":"arXiv - QuanBio - Subcellular Processes","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141503170","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Johannes Keisers, Lorenzo Vito Dal Zovo, Norbert Kern, Luca Ciandrini
{"title":"Biologically relevant finite-size effects in a driven lattice gas with particle pausing and dynamical defects","authors":"Johannes Keisers, Lorenzo Vito Dal Zovo, Norbert Kern, Luca Ciandrini","doi":"arxiv-2406.16569","DOIUrl":"https://doi.org/arxiv-2406.16569","url":null,"abstract":"In this article we present a comprehensive study of the totally asymmetric\u0000simple exclusion process with pausing particles (pTASEP), a model initially\u0000introduced to describe RNAP dynamics during transcription. We extend previous\u0000mean-field approaches and demonstrate that the pTASEP is equivalent to the\u0000exclusion process with dynamical defects (ddTASEP), thus broadening the scope\u0000of our investigation to a larger class of problems related to transcription and\u0000translation. We extend the mean-field theory to the open boundary case,\u0000revealing the system's phase diagram and critical values of entry and exit\u0000rates. However, we identify a significant discrepancy between theory and\u0000simulations in a region of the parameter space, indicating severe finite-size\u0000effects. To address this, we develop a single-cluster approximation that\u0000captures the relationship between current and lattice size, providing a more\u0000accurate representation of the system's dynamics. Finally, we extend our\u0000approach to open boundary conditions, demonstrating its applicability in\u0000different scenarios. Our findings underscore the importance of considering\u0000finite-size effects, often overlooked in the literature, when modelling\u0000biological processes such as transcription and translation.","PeriodicalId":501170,"journal":{"name":"arXiv - QuanBio - Subcellular Processes","volume":"16 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141503172","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Eva Martin Solana, Laura Casado Zueras, Teobaldo E. Torres, Gerardo F. Goya, Maria Rosario Fernandez Fernandez, Jose Jesus Fernandez
{"title":"Disruption of the mitochondrial network in a mouse model of Huntington's disease visualized by in tissue multiscale 3D electron microscopy","authors":"Eva Martin Solana, Laura Casado Zueras, Teobaldo E. Torres, Gerardo F. Goya, Maria Rosario Fernandez Fernandez, Jose Jesus Fernandez","doi":"arxiv-2406.16977","DOIUrl":"https://doi.org/arxiv-2406.16977","url":null,"abstract":"Huntington's disease (HD) is an inherited neurodegenerative disorder caused\u0000by an expanded CAG repeat in the coding sequence of the huntingtin protein.\u0000Initially, it predominantly affects medium-sized spiny neurons (MSSNs) of the\u0000corpus striatum. No effective treatment is available, thus urging the\u0000identification of potential therapeutic targets. While evidence of\u0000mitochondrial structural alterations in HD exists, previous studies mainly\u0000employed 2D approaches and were performed outside the strictly native brain\u0000context. In this study, we adopted a novel multiscale approach to conduct a\u0000comprehensive 3D in situ structural analysis of mitochondrial disturbances in a\u0000mouse model of HD. We investigated MSSNs within brain tissue under optimal structural conditions\u0000utilizing state-of-the-art 3D imaging technologies, specifically FIB/SEM for\u0000the complete imaging of neuronal somas and Electron Tomography for detailed\u0000morphological examination and image processing-based quantitative analysis. Our\u0000findings suggest a disruption of the mitochondrial network towards\u0000fragmentation in HD. The network of interlaced, slim, and long mitochondria\u0000observed in healthy conditions transforms into isolated, swollen, and short\u0000entities, with internal cristae disorganization, cavities, and abnormally large\u0000matrix granules.","PeriodicalId":501170,"journal":{"name":"arXiv - QuanBio - Subcellular Processes","volume":"20 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141503171","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Methylglyoxal induces cardiac dysfunction through mechanisms involving altered intracellular calcium handling in the rat heart","authors":"Hélène PeyretPPF, Céline KoneckiPPF, CHU Reims, Christine TerrynPICT, Florine DubuissonPPF, Hervé MillartPPF, Catherine FeliuPPF, CHU Reims, Zoubir DjeradaPPF, CHU Reims","doi":"arxiv-2406.14034","DOIUrl":"https://doi.org/arxiv-2406.14034","url":null,"abstract":"Methylglyoxal (MGO) is an endogenous, highly reactive dicarbonyl metabolite\u0000generated under hyperglycaemic conditions. MGO plays a role in developing\u0000pathophysiological conditions, including diabetic cardiomyopathy. However, the\u0000mechanisms involved and the molecular targets of MGO in the heart have not been\u0000elucidated. In this work, we studied the exposure-related effects of MGO on\u0000cardiac function in an isolated perfused rat heart ex vivo model. The effect of\u0000MGO on calcium homeostasis in cardiomyocytes was studied in vitro by the\u0000fluorescence indicator of intracellular calcium Fluo-4. We demonstrated that\u0000MGO induced cardiac dysfunction, both in contractility and diastolic function.\u0000In rat heart, the effects of MGO treatment were significantly limited by\u0000aminoguanidine, a scavenger of MGO, ruthenium red, a general cation channel\u0000blocker, and verapamil, an L-type voltage-dependent calcium channel blocker,\u0000demonstrating that this dysfunction involved alteration of calcium regulation.\u0000MGO induced a significant concentration-dependent increase of intracellular\u0000calcium in neonatal rat cardiomyocytes, which was limited by aminoguanidine and\u0000verapamil. These results suggest that the functionality of various calcium\u0000channels is altered by MGO, particularly the L-type calcium channel, thus\u0000explaining its cardiac toxicity. Therefore, MGO could participate in the\u0000development of diabetic cardiomyopathy through its impact on calcium\u0000homeostasis in cardiac cells.","PeriodicalId":501170,"journal":{"name":"arXiv - QuanBio - Subcellular Processes","volume":"341 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141503173","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yuan-Nan Young, Vicente Gomez Herrera, Helena Z. Huan, Reza Farhadifar, Michael J. Shelley
{"title":"A first-principles geometric model for dynamics of motor-driven centrosomal asters","authors":"Yuan-Nan Young, Vicente Gomez Herrera, Helena Z. Huan, Reza Farhadifar, Michael J. Shelley","doi":"arxiv-2406.14350","DOIUrl":"https://doi.org/arxiv-2406.14350","url":null,"abstract":"The centrosomal aster is a mobile cellular organelle that exerts and\u0000transmits forces necessary for nuclear migration and spindle positioning.\u0000Recent experimental and theoretical studies of nematode and human cells\u0000demonstrate that pulling forces on asters by cortical force generators are\u0000dominant during such processes. We present a comprehensive investigation of a\u0000first-principles model of aster dynamics, the S-model (S for stoichiometry),\u0000based solely on such forces. The model evolves the astral centrosome position,\u0000a probability field of cell-surface motor occupancy by centrosomal microtubules\u0000(under an assumption of stoichiometric binding), and free boundaries of\u0000unattached, growing microtubules. We show how cell shape affects the centering\u0000stability of the aster, and its transition to oscillations with increasing\u0000motor number. Seeking to understand observations in single-cell nematode\u0000embryos, we use accurate simulations to examine the nonlinear structures of the\u0000bifurcations, and demonstrate the importance of binding domain overlap to\u0000interpreting genetic perturbation experiments. We find a rich dynamical\u0000landscape, dependent upon cell shape, such as internal equatorial orbits of\u0000asters that can be seen as traveling wave solutions. Finally, we study the\u0000interactions of multiple asters and demonstrate an effective mutual repulsion\u0000due to their competition for cortical force generators. We find, amazingly,\u0000that asters can relax onto the vertices of platonic and non-platonic solids,\u0000closely mirroring the results of the classical Thomson problem for\u0000energy-minimizing configurations of electrons constrained to a sphere and\u0000interacting via repulsive Coulomb potentials. Our findings both explain\u0000experimental observations, providing insights into the mechanisms governing\u0000spindle positioning and cell division dynamics, and show the possibility of new\u0000nonlinear phenomena in cell biology.","PeriodicalId":501170,"journal":{"name":"arXiv - QuanBio - Subcellular Processes","volume":"21 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141503175","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Large Deviations of Piecewise-Deterministic-Markov-Processes with Application to Stochastic Calcium Waves","authors":"Gaetan Barbet, James MacLaurin, Moshe Silverstein","doi":"arxiv-2406.12493","DOIUrl":"https://doi.org/arxiv-2406.12493","url":null,"abstract":"We prove a Large Deviation Principle for Piecewise Deterministic Markov\u0000Processes (PDMPs). This is an asymptotic estimate for the probability of a\u0000trajectory in the large size limit. Explicit Euler-Lagrange equations are\u0000determined for computing optimal first-hitting-time trajectories. The results\u0000are applied to a model of stochastic calcium dynamics. It is widely conjectured\u0000that the mechanism of calcium puff generation is a multiscale process: with\u0000microscopic stochastic fluctuations in the opening and closing of individual\u0000channels generating cell-wide waves via the diffusion of calcium and other\u0000signaling molecules. We model this system as a PDMP, with $N gg 1$ stochastic\u0000calcium channels that are coupled via the ambient calcium concentration. We\u0000employ the Large Deviations theory to estimate the probability of cell-wide\u0000calcium waves being produced through microscopic stochasticity.","PeriodicalId":501170,"journal":{"name":"arXiv - QuanBio - Subcellular Processes","volume":"18 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141531078","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Teena tom Dieck, Lukas Brand, Sebastian Lotter, Kathrin Castiglione, Robert Schober, Maximilian Schäfer
{"title":"Nanoscale Transmitters Employing Cooperative Transmembrane Transport Proteins for Molecular Communication","authors":"Teena tom Dieck, Lukas Brand, Sebastian Lotter, Kathrin Castiglione, Robert Schober, Maximilian Schäfer","doi":"arxiv-2406.06147","DOIUrl":"https://doi.org/arxiv-2406.06147","url":null,"abstract":"This paper introduces a novel optically controllable molecular communication\u0000(MC) transmitter (TX) design, which is based on a vesicular nanodevice (ND)\u0000functionalized for the release of signaling molecules via transmembrane\u0000proteins. Due to its optical-to-chemical conversion capability, the ND can be\u0000used as an externally controllable TX for several MC applications such as bit\u0000transmission and targeted drug delivery. The proposed TX design comprises two\u0000cooperating modules, an energizing module and a release module, and depending\u0000on the specific choices for the modules allows for the release of different\u0000types of signaling molecules. After setting up a general system model for the\u0000proposed TX design, we conduct a detailed mathematical analysis of a specific\u0000realization. In particular, we derive an exact analytical and an approximate\u0000closed-form solution for the concentration of the released signaling molecules\u0000and validate our results by comparison with a numerical solution. Moreover, we\u0000consider the impact of a buffering medium, which is typically present in\u0000experimental and application environments, in both our analytical and numerical\u0000analyses to evaluate the feasibility of our proposed TX design for practical\u0000chemical implementation. The proposed analytical and closed-form models\u0000facilitate system parameter optimization, which can accelerate the experimental\u0000development cycle of the proposed ND architecture in the future.","PeriodicalId":501170,"journal":{"name":"arXiv - QuanBio - Subcellular Processes","volume":"81 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141503174","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"A story of cooperation: Centrosome-cytoskeleton interactions and implications","authors":"Subarna Dutta, Arnab Barua","doi":"arxiv-2406.06135","DOIUrl":"https://doi.org/arxiv-2406.06135","url":null,"abstract":"A structural link between cell's centrosome and cytoskeleton has been\u0000proposed years ago. Centrosomes are usually located in the proximity to the\u0000nuclei and maintain nucleus-centrosome axis. This positioning aids in\u0000determining the polarity of interphase cells and ensure spindle assembly in\u0000mitotic cells. Centrosome also maintains physical interaction with different\u0000forms of cytoskeleton to trade-off between internal architecture and cell\u0000polarity in tissue specific as well as development specific manner. Several\u0000crosslinkers are also available to support this interaction and consequently\u0000promote cytoskeleton nucleation as well as centrosome nucleation. We present an\u0000overview of coordinated action of cytoskeletal elements on centrosomes and vice\u0000versa to modulate complex cellular functions, as diverse as cell migration,\u0000cell adhesion and cell division.","PeriodicalId":501170,"journal":{"name":"arXiv - QuanBio - Subcellular Processes","volume":"31 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141503176","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}