Physical biology最新文献_第3页

An exploration of the binding prediction of anatoxin-a and atropine to acetylcholinesterase enzyme using multi-level computer simulations. 利用多层次计算机模拟探索阿那托毒素a和阿托品与乙酰胆碱酯酶的结合预测。

IF 2 4区生物学

Physical biology Pub Date : 2023-11-23 DOI: 10.1088/1478-3975/ad0caa

Showkat Ahmad Mir, Jamoliddin Razzokov, Vishwajeet Mukherjee, Iswar Baitharu, Binata Nayak

{"title":"An exploration of the binding prediction of anatoxin-a and atropine to acetylcholinesterase enzyme using multi-level computer simulations.","authors":"Showkat Ahmad Mir, Jamoliddin Razzokov, Vishwajeet Mukherjee, Iswar Baitharu, Binata Nayak","doi":"10.1088/1478-3975/ad0caa","DOIUrl":"10.1088/1478-3975/ad0caa","url":null,"abstract":"Acetylcholinesterase (AChE) is crucial for the breakdown of acetylcholine to acetate and choline, while the inhibition of AChE by anatoxin-a (ATX-a) results in severe health complications. This study explores the structural characteristics of ATX-a and its interactions with AChE, comparing to the reference molecule atropine for binding mechanisms. Molecular docking simulations reveal strong binding affinity of both ATX-a and atropine to AChE, interacting effectively with specific amino acids in the binding site as potential inhibitors. Quantitative assessment using the MM-PBSA method demonstrates a significantly negative binding free energy of −81.659 kJ mol−1 for ATX-a, indicating robust binding, while atropine exhibits a stronger binding affinity with a free energy of −127.565 kJ mol−1. Umbrella sampling calculates the ΔG bind values to evaluate binding free energies, showing a favorable ΔG bind of −36.432 kJ mol−1 for ATX-a and a slightly lower value of −30.12 kJ mol−1 for atropine. This study reveals the dual functionality of ATX-a, acting as both a nicotinic acetylcholine receptor agonist and an AChE inhibitor. Remarkably, stable complexes form between ATX-a and atropine with AChE at its active site, exhibiting remarkable binding free energies. These findings provide valuable insights into the potential use of ATX-a and atropine as promising candidates for modulating AChE activity.","PeriodicalId":20207,"journal":{"name":"Physical biology","volume":null,"pages":null},"PeriodicalIF":2.0,"publicationDate":"2023-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"107592072","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Calcium regulates cortex contraction inPhysarum polycephalum. 钙调节多头绒泡菌皮层收缩。

IF 2 4区生物学

Physical biology Pub Date : 2023-11-17 DOI: 10.1088/1478-3975/ad0a9a

Bjoern Kscheschinski, Mirna Kramar, Karen Alim

{"title":"Calcium regulates cortex contraction inPhysarum polycephalum.","authors":"Bjoern Kscheschinski, Mirna Kramar, Karen Alim","doi":"10.1088/1478-3975/ad0a9a","DOIUrl":"10.1088/1478-3975/ad0a9a","url":null,"abstract":"The tubular network-forming slime moldPhysarum polycephalumis able to maintain long-scale contraction patterns driven by an actomyosin cortex. The resulting shuttle streaming in the network is crucial for the organism to respond to external stimuli and reorganize its body mass giving rise to complex behaviors. However, the chemical basis of the self-organized flow pattern is not fully understood. Here, we present ratiometric measurements of free intracellular calcium in simple morphologies ofPhysarumnetworks. The spatiotemporal patterns of the free calcium concentration reveal a nearly anti-correlated relation to the tube radius, suggesting that calcium is indeed a key regulator of the actomyosin activity. We compare the experimentally observed phase relation between the radius and the calcium concentration to the predictions of a theoretical model including calcium as an inhibitor. Numerical simulations of the model suggest that calcium indeed inhibits the contractions inPhysarum, although a quantitative difference to the experimentally measured phase relation remains. Unraveling the mechanism underlying the contraction patterns is a key step in gaining further insight into the principles ofPhysarum's complex behavior.","PeriodicalId":20207,"journal":{"name":"Physical biology","volume":null,"pages":null},"PeriodicalIF":2.0,"publicationDate":"2023-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136398857","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

High-throughput design of cultured tissue moulds using a biophysical model: optimising cell alignment. 使用生物物理模型对培养的组织模具进行高通量设计：优化细胞排列。

IF 2 4区生物学

Physical biology Pub Date : 2023-10-30 DOI: 10.1088/1478-3975/ad0276

James P Hague, Allison E Andrews, Hugh Dickinson

{"title":"High-throughput design of cultured tissue moulds using a biophysical model: optimising cell alignment.","authors":"James P Hague, Allison E Andrews, Hugh Dickinson","doi":"10.1088/1478-3975/ad0276","DOIUrl":"https://doi.org/10.1088/1478-3975/ad0276","url":null,"abstract":"The technique presented here identifies tethered mould designs, optimised for growing cultured tissue with very highly-aligned cells. It is based on a microscopic biophysical model for polarised cellular hydrogels. There is an unmet need for tools to assist mould and scaffold designs for the growth of cultured tissues with bespoke cell organisations, that can be used in applications such as regenerative medicine, drug screening and cultured meat. High-throughput biophysical calculations were made for a wide variety of computer-generated moulds, with cell-matrix interactions and tissue-scale forces simulated using a contractile network dipole orientation model. Elongated moulds with central broadening and one of the following tethering strategies are found to lead to highly-aligned cells: (1) tethers placed within the bilateral protrusions resulting from an indentation on the short edge, to guide alignment (2) tethers placed within a single vertex to shrink the available space for misalignment. As such, proof-of-concept has been shown for mould and tethered scaffold design based on a recently developed biophysical model. The approach is applicable to a broad range of cell types that align in tissues and is extensible for 3D scaffolds.","PeriodicalId":20207,"journal":{"name":"Physical biology","volume":null,"pages":null},"PeriodicalIF":2.0,"publicationDate":"2023-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71413619","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1

Rapid prediction of lab-grown tissue properties using deep learning. 使用深度学习快速预测实验室培养的组织特性。

IF 2 4区生物学

Physical biology Pub Date : 2023-10-19 DOI: 10.1088/1478-3975/ad0019

Allison Andrews, Hugh Dickinson, James Peter Hague

{"title":"Rapid prediction of lab-grown tissue properties using deep learning.","authors":"Allison Andrews, Hugh Dickinson, James Peter Hague","doi":"10.1088/1478-3975/ad0019","DOIUrl":"10.1088/1478-3975/ad0019","url":null,"abstract":"The interactions between cells and the extracellular matrix are vital for the self-organisation of tissues. In this paper we present proof-of-concept to use machine learning tools to predict the role of this mechanobiology in the self-organisation of cell-laden hydrogels grown in tethered moulds. We develop a process for the automated generation of mould designs with and without key symmetries. We create a large training set withN = 6400 cases by running detailed biophysical simulations of cell-matrix interactions using the contractile network dipole orientation model for the self-organisation of cellular hydrogels within these moulds. These are used to train an implementation of thepix2pixdeep learning model, with an additional 100 cases that were unseen in the training of the neural network for review and testing of the trained model. Comparison between the predictions of the machine learning technique and the reserved predictions from the biophysical algorithm show that the machine learning algorithm makes excellent predictions. The machine learning algorithm is significantly faster than the biophysical method, opening the possibility of very high throughput rational design of moulds for pharmaceutical testing, regenerative medicine and fundamental studies of biology. Future extensions for scaffolds and 3D bioprinting will open additional applications.","PeriodicalId":20207,"journal":{"name":"Physical biology","volume":null,"pages":null},"PeriodicalIF":2.0,"publicationDate":"2023-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41176979","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1

Calcium storage in multivesicular endo-lysosome. 钙在多泡内溶酶体中的储存。

IF 2 4区生物学

Physical biology Pub Date : 2023-10-17 DOI: 10.1088/1478-3975/acfe6a

Cameron C Scott, Vaibhav Wasnik, Paula Nunes-Hassler, Nicolas Demaurex, Karsten Kruse, Jean Gruenberg

{"title":"Calcium storage in multivesicular endo-lysosome.","authors":"Cameron C Scott, Vaibhav Wasnik, Paula Nunes-Hassler, Nicolas Demaurex, Karsten Kruse, Jean Gruenberg","doi":"10.1088/1478-3975/acfe6a","DOIUrl":"10.1088/1478-3975/acfe6a","url":null,"abstract":"It is now established that endo-lysosomes, also referred to as late endosomes, serve as intracellular calcium store, in addition to the endoplasmic reticulum. While abundant calcium-binding proteins provide the latter compartment with its calcium storage capacity, essentially nothing is known about the mechanism responsible for calcium storage in endo-lysosomes. In this paper, we propose that the structural organization of endo-lysosomal membranes drives the calcium storage capacity of the compartment. Indeed, endo-lysosomes exhibit a characteristic multivesicular ultrastructure, with intralumenal membranes providing a large amount of additional bilayer surface. We used a theoretical approach to investigate the calcium storage capacity of endosomes, using known calcium binding affinities for bilayers and morphological data on endo-lysosome membrane organization. Finally, we tested our predictions experimentally after Sorting Nexin 3 depletion to decrease the intralumenal membrane content. We conclude that the major negatively-charge lipids and proteins of endo-lysosomes serve as calcium-binding molecules in the acidic calcium stores of mammalian cells, while the large surface area of intralumenal membranes provide the necessary storage capacity.","PeriodicalId":20207,"journal":{"name":"Physical biology","volume":null,"pages":null},"PeriodicalIF":2.0,"publicationDate":"2023-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41131268","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Seeking and sharing information in collective olfactory search. 在集体嗅觉搜索中寻求和共享信息。

IF 2 4区生物学

Physical biology Pub Date : 2023-10-09 DOI: 10.1088/1478-3975/acfd7a

Emanuele Panizon, Antonio Celani

引用次数: 0

Facilitating cell segmentation with the projection-enhancement network. 利用投影增强网络促进细胞分割。

IF 2 4区生物学

Physical biology Pub Date : 2023-10-09 DOI: 10.1088/1478-3975/acfe53

Christopher Z Eddy, Austin Naylor, Christian T Cunningham, Bo Sun

{"title":"Facilitating cell segmentation with the projection-enhancement network.","authors":"Christopher Z Eddy, Austin Naylor, Christian T Cunningham, Bo Sun","doi":"10.1088/1478-3975/acfe53","DOIUrl":"10.1088/1478-3975/acfe53","url":null,"abstract":"Contemporary approaches to instance segmentation in cell science use 2D or 3D convolutional networks depending on the experiment and data structures. However, limitations in microscopy systems or efforts to prevent phototoxicity commonly require recording sub-optimally sampled data that greatly reduces the utility of such 3D data, especially in crowded sample space with significant axial overlap between objects. In such regimes, 2D segmentations are both more reliable for cell morphology and easier to annotate. In this work, we propose the projection enhancement network (PEN), a novel convolutional module which processes the sub-sampled 3D data and produces a 2D RGB semantic compression, and is trained in conjunction with an instance segmentation network of choice to produce 2D segmentations. Our approach combines augmentation to increase cell density using a low-density cell image dataset to train PEN, and curated datasets to evaluate PEN. We show that with PEN, the learned semantic representation in CellPose encodes depth and greatly improves segmentation performance in comparison to maximum intensity projection images as input, but does not similarly aid segmentation in region-based networks like Mask-RCNN. Finally, we dissect the segmentation strength against cell density of PEN with CellPose on disseminated cells from side-by-side spheroids. We present PEN as a data-driven solution to form compressed representations of 3D data that improve 2D segmentations from instance segmentation networks.","PeriodicalId":20207,"journal":{"name":"Physical biology","volume":null,"pages":null},"PeriodicalIF":2.0,"publicationDate":"2023-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10586931/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41156771","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Quantitative insights in tissue growth and morphogenesis with optogenetics. 光遗传学对组织生长和形态发生的定量见解。

IF 2 4区生物学

Physical biology Pub Date : 2023-09-28 DOI: 10.1088/1478-3975/acf7a1

Mayesha Sahir Mim, Caroline Knight, Jeremiah J Zartman

{"title":"Quantitative insights in tissue growth and morphogenesis with optogenetics.","authors":"Mayesha Sahir Mim, Caroline Knight, Jeremiah J Zartman","doi":"10.1088/1478-3975/acf7a1","DOIUrl":"10.1088/1478-3975/acf7a1","url":null,"abstract":"Cells communicate with each other to jointly regulate cellular processes during cellular differentiation and tissue morphogenesis. This multiscale coordination arises through the spatiotemporal activity of morphogens to pattern cell signaling and transcriptional factor activity. This coded information controls cell mechanics, proliferation, and differentiation to shape the growth and morphogenesis of organs. While many of the molecular components and physical interactions have been identified in key model developmental systems, there are still many unresolved questions related to the dynamics involved due to challenges in precisely perturbing and quantitatively measuring signaling dynamics. Recently, a broad range of synthetic optogenetic tools have been developed and employed to quantitatively define relationships between signal transduction and downstream cellular responses. These optogenetic tools can control intracellular activities at the single cell or whole tissue scale to direct subsequent biological processes. In this brief review, we highlight a selected set of studies that develop and implement optogenetic tools to unravel quantitative biophysical mechanisms for tissue growth and morphogenesis across a broad range of biological systems through the manipulation of morphogens, signal transduction cascades, and cell mechanics. More generally, we discuss how optogenetic tools have emerged as a powerful platform for probing and controlling multicellular development.","PeriodicalId":20207,"journal":{"name":"Physical biology","volume":null,"pages":null},"PeriodicalIF":2.0,"publicationDate":"2023-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10594237/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10181059","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Universal calcium fluctuations inHydramorphogenesis. 水合形态发生中普遍存在的钙波动。

IF 2 4区生物学

Physical biology Pub Date : 2023-09-22 DOI: 10.1088/1478-3975/acf8a4

Oded Agam, Erez Braun

{"title":"Universal calcium fluctuations inHydramorphogenesis.","authors":"Oded Agam, Erez Braun","doi":"10.1088/1478-3975/acf8a4","DOIUrl":"10.1088/1478-3975/acf8a4","url":null,"abstract":"Understanding the collective physical processes that drive robust morphological transitions in animal development necessitates the characterization of the relevant fields involved in morphogenesis. Calcium (Ca2+) is recognized as one such field. In this study, we demonstrate that the spatial fluctuations of Ca2+duringHydraregeneration exhibit universal characteristics. To investigate this phenomenon, we employ two distinct controls, an external electric field andheptanol, a gap junction-blocking drug. Both lead to the modulation of the Ca2+activity and a reversible halting of the regeneration process. The application of an electric field enhances Ca2+activity in theHydra's tissue and increases its spatial correlations, while the administration ofheptanolinhibits its activity and diminishes the spatial correlations. Remarkably, the statistical characteristics of Ca2+spatial fluctuations, including the coefficient of variation and skewness, manifest universal shape distributions across tissue samples and conditions. We introduce a field-theoretic model, describing fluctuations in a tilted double-well potential, which successfully captures these universal properties. Moreover, our analysis reveals that the Ca2+activity is spatially localized, and theHydra's tissue operates near the onset of bistability, where the local Ca2+activity fluctuates between low and high excited states in distinct regions. These findings highlight the prominent role of the Ca2+field inHydramorphogenesis and provide insights into the underlying mechanisms governing robust morphological transitions.","PeriodicalId":20207,"journal":{"name":"Physical biology","volume":null,"pages":null},"PeriodicalIF":2.0,"publicationDate":"2023-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10215486","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1

EMT induces characteristic changes of Rho GTPases and downstream effectors with a mitosis-specific twist. EMT通过有丝分裂特异性扭曲诱导Rho-GTP酶和下游效应物的特征性变化。

IF 2 4区生物学

Physical biology Pub Date : 2023-09-12 DOI: 10.1088/1478-3975/acf5bd

Kamran Hosseini, Annika Frenzel, Elisabeth Fischer-Friedrich

{"title":"EMT induces characteristic changes of Rho GTPases and downstream effectors with a mitosis-specific twist.","authors":"Kamran Hosseini, Annika Frenzel, Elisabeth Fischer-Friedrich","doi":"10.1088/1478-3975/acf5bd","DOIUrl":"10.1088/1478-3975/acf5bd","url":null,"abstract":"Epithelial-mesenchymal transition (EMT) is a key cellular transformation for many physiological and pathological processes ranging from cancer over wound healing to embryogenesis. Changes in cell migration, cell morphology and cellular contractility were identified as hallmarks of EMT. These cellular properties are known to be tightly regulated by the actin cytoskeleton. EMT-induced changes of actin-cytoskeletal regulation were demonstrated by previous reports of changes of actin cortex mechanics in conjunction with modifications of cortex-associated f-actin and myosin. However, at the current state, the changes of upstream actomyosin signaling that lead to corresponding mechanical and compositional changes of the cortex are not well understood. In this work, we show in breast epithelial cancer cells MCF-7 that EMT results in characteristic changes of the cortical association of Rho-GTPases Rac1, RhoA and RhoC and downstream actin regulators cofilin, mDia1 and Arp2/3. In the light of our findings, we propose that EMT-induced changes in cortical mechanics rely on two hitherto unappreciated signaling paths-i) an interaction between Rac1 and RhoC and ii) an inhibitory effect of Arp2/3 activity on cortical association of myosin II.","PeriodicalId":20207,"journal":{"name":"Physical biology","volume":null,"pages":null},"PeriodicalIF":2.0,"publicationDate":"2023-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10222964","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0