Biophysical journal最新文献

{"title":"Interfacial energy constraints are sufficient to align cells over large distances.","authors":"Sham Tlili, Murat Shagirov, Shaobo Zhang, Timothy E Saunders","doi":"10.1016/j.bpj.2025.02.011","DOIUrl":"10.1016/j.bpj.2025.02.011","url":null,"abstract":"<p><p>During development and wound healing, cells need to form long-range ordered structures to ensure precise formation of organs and repair damage. This requires cells to locate specific partner cells to which to adhere. How such cell matching reliably happens is an open problem, particularly in the presence of biological variability. Here, we use an equilibrium energy model to simulate how cell matching can occur with subcellular precision. A single parameter-encapsulating the competition between selective cell adhesion and cell compressibility-can reproduce experimental observations of cell alignment in the Drosophila embryonic heart. This demonstrates that adhesive differences between cells (in the case of the heart, mediated by filopodia interactions) are sufficient to drive cell matching without requiring cell rearrangements. The biophysical model can explain observed matching defects in mutant conditions and when there is significant biological variability. Using a dynamic vertex model, we demonstrate the existence of an optimal range of effective cell rigidities for efficient matching. Overall, this work shows that equilibrium energy considerations are consistent with observed cell matching in cardioblasts and has potential application to other systems, such as neuron connections and wound repair.</p>","PeriodicalId":8922,"journal":{"name":"Biophysical journal","volume":" ","pages":"1011-1023"},"PeriodicalIF":3.2,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11947472/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143623371","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Quantifying cell cycle regulation by tissue crowding.","authors":"Carles Falcó, Daniel J Cohen, José A Carrillo, Ruth E Baker","doi":"10.1016/j.bpj.2024.05.003","DOIUrl":"10.1016/j.bpj.2024.05.003","url":null,"abstract":"<p><p>The spatiotemporal coordination and regulation of cell proliferation is fundamental in many aspects of development and tissue maintenance. Cells have the ability to adapt their division rates in response to mechanical constraints, yet we do not fully understand how cell proliferation regulation impacts cell migration phenomena. Here, we present a minimal continuum model of cell migration with cell cycle dynamics, which includes density-dependent effects and hence can account for cell proliferation regulation. By combining minimal mathematical modeling, Bayesian inference, and recent experimental data, we quantify the impact of tissue crowding across different cell cycle stages in epithelial tissue expansion experiments. Our model suggests that cells sense local density and adapt cell cycle progression in response, during G1 and the combined S/G2/M phases, providing an explicit relationship between each cell-cycle-stage duration and local tissue density, which is consistent with several experimental observations. Finally, we compare our mathematical model's predictions to different experiments studying cell cycle regulation and present a quantitative analysis on the impact of density-dependent regulation on cell migration patterns. Our work presents a systematic approach for investigating and analyzing cell cycle data, providing mechanistic insights into how individual cells regulate proliferation, based on population-based experimental measurements.</p>","PeriodicalId":8922,"journal":{"name":"Biophysical journal","volume":" ","pages":"923-932"},"PeriodicalIF":3.2,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11947467/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140875747","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanical strengthening of cell-cell adhesion during mouse embryo compaction.","authors":"Ludmilla de Plater, Julie Firmin, Jean-Léon Maître","doi":"10.1016/j.bpj.2024.03.028","DOIUrl":"10.1016/j.bpj.2024.03.028","url":null,"abstract":"<p><p>Compaction is the first morphogenetic movement of the eutherian mammals and involves a developmentally regulated adhesion process. Previous studies investigated cellular and mechanical aspects of compaction. During mouse and human compaction, cells spread onto each other as a result of a contractility-mediated increase in surface tension pulling at the edges of their cell-cell contacts. However, how compaction may affect the mechanical stability of cell-cell contacts remains unknown. Here, we used a dual pipette aspiration assay on cell doublets to quantitatively analyze the mechanical stability of compacting mouse embryos. We measured increased mechanical stability of contacts with rupture forces growing from 40 to 70 nN, which was highly correlated with cell-cell contact expansion. Analyzing the dynamic molecular reorganization of cell-cell contacts, we find minimal recruitment of the cell-cell adhesion molecule Cdh1 (also known as E-cadherin) to contacts but we observe its reorganization into a peripheral adhesive ring. However, this reorganization is not associated with increased effective bond density, contrary to previous reports in other adhesive systems. Using genetics, we reduce the levels of Cdh1 or replace it with a chimeric adhesion molecule composed of the extracellular domain of Cdh1 and the intracellular domain of Cdh2 (also known as N-cadherin). We find that reducing the levels of Cdh1 impairs the mechanical stability of cell-cell contacts due to reduced contact growth, which nevertheless show higher effective bond density than wild-type contacts of similar size. On the other hand, chimeric adhesion molecules cannot form large or strong contacts indicating that the intracellular domain of Cdh2 is unable to reorganize contacts and/or is mechanically weaker than the one of Cdh1 in mouse embryos. Together, we find that mouse embryo compaction mechanically strengthens cell-cell adhesion via the expansion of Cdh1 adhesive rings that maintain pre-compaction levels of effective bond density.</p>","PeriodicalId":8922,"journal":{"name":"Biophysical journal","volume":" ","pages":"901-912"},"PeriodicalIF":3.2,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11947474/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140288159","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Both the transcriptional activator, Bcd, and repressor, Cic, form small mobile oligomeric clusters.","authors":"Lili Zhang, Lydia Hodgins, Shariful Sakib, Alexander Verbeem, Ahmad Mahmood, Carmina Perez-Romero, Robert A Marmion, Nathalie Dostatni, Cécile Fradin","doi":"10.1016/j.bpj.2024.08.011","DOIUrl":"10.1016/j.bpj.2024.08.011","url":null,"abstract":"<p><p>Transcription factors play an essential role in pattern formation during early embryo development, generating a strikingly fast and precise transcriptional response that results in sharp gene expression boundaries. To characterize the steps leading up to transcription, we performed a side-by-side comparison of the nuclear dynamics of two morphogens, a transcriptional activator, Bicoid (Bcd), and a transcriptional repressor, Capicua (Cic), both involved in body patterning along the anterior-posterior axis of the early Drosophila embryo. We used a combination of fluorescence recovery after photobleaching, fluorescence correlation spectroscopy, and single-particle tracking to access a wide range of dynamical timescales. Despite their opposite effects on gene transcription, we find that Bcd and Cic have very similar nuclear dynamics, characterized by the coexistence of a freely diffusing monomer population with a number of oligomeric clusters, which range from low stoichiometry and high mobility clusters to larger, DNA-bound hubs. Our observations are consistent with the inclusion of both Bcd and Cic into transcriptional hubs or condensates, while putting constraints on the mechanism by which these form. These results fit in with the recent proposal that many transcription factors might share a common search strategy for target gene regulatory regions that makes use of their large unstructured regions, and may eventually help explain how the transcriptional response they elicit can be at the same time so fast and so precise.</p>","PeriodicalId":8922,"journal":{"name":"Biophysical journal","volume":" ","pages":"980-995"},"PeriodicalIF":3.2,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11947476/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142008223","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The ATPase asymmetry: Novel computational insight into coupling diverse F_O motors with tripartite F₁.","authors":"Shintaroh Kubo, Yasushi Okada","doi":"10.1016/j.bpj.2024.03.013","DOIUrl":"10.1016/j.bpj.2024.03.013","url":null,"abstract":"<p><p>ATP synthase, a crucial enzyme for cellular bioenergetics, operates via the coordinated coupling of an F_O motor, which presents variable symmetry, and a tripartite F₁ motor. Despite extensive research, the understanding of their coupling dynamics, especially with non-10-fold symmetrical F_O motors, remains incomplete. This study investigates the coupling patterns between eightfold and ninefold F_O motors and the constant threefold F₁ motor using coarse-grained molecular dynamics simulations. We unveil that in the case of a ninefold F_O motor, a 3-3-3 motion is most likely to occur, whereas a 3-3-2 motion predominates with an eightfold F_O motor. Furthermore, our findings propose a revised model for the coupling method, elucidating that the pathways' energy usage is primarily influenced by F₁ rotation and conformational changes hindered by the b-subunits. Our results present a crucial step toward comprehending the energy landscape and mechanisms governing ATP synthase operation.</p>","PeriodicalId":8922,"journal":{"name":"Biophysical journal","volume":" ","pages":"891-900"},"PeriodicalIF":3.2,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11947463/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140064710","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Kismet/CHD7/CHD8 affects gut microbiota, mechanics, and the gut-brain axis in Drosophila melanogaster.","authors":"Angelo Niosi, Nguyên Henry Võ, Punithavathi Sundaramurthy, Chloe Welch, Aliyah Penn, Yelena Yuldasheva, Adam Alfareh, Kaitlyn Rausch, Takhmina Amin-Rahbar, Jeffery Cavanaugh, Prince Yadav, Stephanie Peterson, Raina Brown, Alain Hu, Any Ardon-Castro, Darren Nguyen, Robert Crawford, Wendy Lee, Eliza J Morris, Mikkel Herholdt Jensen, Kimberly Mulligan","doi":"10.1016/j.bpj.2024.06.016","DOIUrl":"10.1016/j.bpj.2024.06.016","url":null,"abstract":"<p><p>The gut microbiome affects brain and neuronal development and may contribute to the pathophysiology of neurodevelopmental disorders. However, it is unclear how risk genes associated with such disorders affect gut physiology in a manner that could impact microbial colonization and how the mechanical properties of the gut tissue might play a role in gut-brain bidirectional communication. To address this, we used Drosophila melanogaster with a null mutation in the gene kismet, an ortholog of chromodomain helicase DNA-binding protein (CHD) family members CHD7 and CHD8. In humans, these are risk genes for neurodevelopmental disorders with co-occurring gastrointestinal symptoms. We found that kismet mutant flies have a significant increase in gastrointestinal transit time, indicating the functional homology of kismet with CHD7/CHD8 in vertebrates. Rheological characterization of dissected gut tissue revealed significant changes in the mechanics of kismet mutant gut elasticity, strain stiffening behavior, and tensile strength. Using 16S rRNA metagenomic sequencing, we also found that kismet mutants have reduced diversity and abundance of gut microbiota at every taxonomic level. To investigate the connection between the gut microbiome and behavior, we depleted gut microbiota in kismet mutant and control flies and quantified the flies' courtship behavior. Depletion of gut microbiota rescued courtship defects of kismet mutant flies, indicating a connection between gut microbiota and behavior. In striking contrast, depletion of the gut microbiome in the control strain reduced courtship activity, demonstrating that antibiotic treatment can have differential impacts on behavior and may depend on the status of microbial dysbiosis in the gut prior to depletion. We propose that Kismet influences multiple gastrointestinal phenotypes that contribute to the gut-microbiome-brain axis to influence behavior. We also suggest that gut tissue mechanics should be considered as an element in the gut-brain communication loop, both influenced by and potentially influencing the gut microbiome and neurodevelopment.</p>","PeriodicalId":8922,"journal":{"name":"Biophysical journal","volume":" ","pages":"933-941"},"PeriodicalIF":3.2,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11947469/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141431201","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Empirical methods that provide physical descriptions of dynamic cellular processes.","authors":"Ian Seim, Stephan W Grill","doi":"10.1016/j.bpj.2024.12.003","DOIUrl":"10.1016/j.bpj.2024.12.003","url":null,"abstract":"<p><p>We review empirical methods that can be used to provide physical descriptions of dynamic cellular processes during development and disease. Our focus will be nonspatial descriptions and the inference of underlying interaction networks including cell-state lineages, gene regulatory networks, and molecular interactions in living cells. Our overarching questions are: How much can we learn from just observing? To what degree is it possible to infer causal and/or precise mathematical relationships from observations? We restrict ourselves to data sets arising from only observations, or experiments in which minimal perturbations have taken place to facilitate observation of the systems as they naturally occur. We discuss analysis perspectives in order from those offering the least descriptive power but requiring the least assumptions such as statistical associations. We end with those that are most descriptive, but require stricter assumptions and more previous knowledge of the systems such as causal inference and dynamical systems approaches. We hope to provide and encourage the use of a wide array of options for quantitative cell biologists to learn as much as possible from their observations at all stages of understanding of their system of interest. Finally, we provide our own recipe of how to empirically determine quantitative relationships and growth laws from live-cell microscopy data, the resultant predictions of which can then be verified with perturbation experiments. We also include an extended supplement that describes further inference algorithms and theory for the interested reader.</p>","PeriodicalId":8922,"journal":{"name":"Biophysical journal","volume":" ","pages":"861-875"},"PeriodicalIF":3.2,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11947468/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142784043","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Developmental biophysics.","authors":"Thorsten Wohland, Timothy E Saunders, Chii Jou Chan","doi":"10.1016/j.bpj.2025.02.009","DOIUrl":"10.1016/j.bpj.2025.02.009","url":null,"abstract":"","PeriodicalId":8922,"journal":{"name":"Biophysical journal","volume":" ","pages":"E1-E2"},"PeriodicalIF":3.2,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11947461/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143522523","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fine-tuning of Fgf8 morphogen gradient by heparan sulfate proteoglycans in the extracellular matrix.","authors":"Mansi Gupta, Thomas Kurth, Fabian Heinemann, Petra Schwille, Sebastian Keil, Franziska Knopf, Michael Brand","doi":"10.1016/j.bpj.2024.12.009","DOIUrl":"10.1016/j.bpj.2024.12.009","url":null,"abstract":"<p><p>Embryonic development is orchestrated by the action of morphogens, which spread out from a local source and activate, in a field of target cells, different cellular programs based on their concentration gradient. Fibroblast growth factor 8 (Fgf8) is a morphogen with important functions in embryonic organizing centers. It forms a gradient in the extracellular space by free diffusion, interaction with the extracellular matrix (ECM), and receptor-mediated endocytosis. However, morphogen gradient regulation by ECM is still poorly understood. Here, we show that specific heparan sulfate proteoglycans (HSPGs) bind Fgf8 with different affinities directly in the ECM of living zebrafish embryos, thus affecting its diffusion and signaling. Using single-molecule fluorescence correlation spectroscopy, we quantify this binding in vivo, and find two different modes of interaction. First, reducing or increasing the concentration of specific HSPGs in the extracellular space alters Fgf8 diffusion and, thus, its gradient shape. Second, ternary complex formation of Fgf8 ligand with Fgf receptors and HSPGs at the cell surface requires HSPG attachment to the cell membrane. Together, our results show that graded Fgf8 morphogen distribution is achieved by constraining free Fgf8 diffusion through successive interactions with HSPGs at the cell surface and in ECM space.</p>","PeriodicalId":8922,"journal":{"name":"Biophysical journal","volume":" ","pages":"996-1010"},"PeriodicalIF":3.2,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11947464/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142817036","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Locally fast, globally slow.","authors":"Pierre Recouvreux","doi":"10.1016/j.bpj.2024.07.022","DOIUrl":"10.1016/j.bpj.2024.07.022","url":null,"abstract":"","PeriodicalId":8922,"journal":{"name":"Biophysical journal","volume":" ","pages":"859-860"},"PeriodicalIF":3.2,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11947462/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141733492","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}