Biophysical journalPub Date : 2025-03-18Epub Date: 2024-06-20DOI: 10.1016/j.bpj.2024.06.017
João R D Ramos, Blanca Jazmin Reyes-Hernández, Karen Alim, Alexis Maizel
{"title":"Auxin-mediated stress relaxation in pericycle and endoderm remodeling drives lateral root initiation.","authors":"João R D Ramos, Blanca Jazmin Reyes-Hernández, Karen Alim, Alexis Maizel","doi":"10.1016/j.bpj.2024.06.017","DOIUrl":"10.1016/j.bpj.2024.06.017","url":null,"abstract":"<p><p>Plant development relies on the precise coordination of cell growth, which is influenced by the mechanical constraints imposed by rigid cell walls. The hormone auxin plays a crucial role in regulating this growth by altering the mechanical properties of cell walls. During the postembryonic formation of lateral roots, pericycle cells deep within the main root are triggered by auxin to resume growth and divide to form a new root. This growth involves a complex interplay between auxin, growth, and the resolution of mechanical conflicts with the overlying endodermis. However, the exact mechanisms by which this coordination is achieved are still unknown. Here, we propose a model that integrates tissue mechanics and auxin transport, revealing a connection between the auxin-induced relaxation of mechanical stress in the pericycle and auxin signaling in the endodermis. We show that the endodermis initially limits the growth of pericycle cells, resulting in a modest initial expansion. However, the associated stress relaxation is sufficient to redirect auxin to the overlying endodermis, which then actively accommodates the growth, allowing for the subsequent development of the lateral root. Our model uncovers that increased pericycle turgor and decreased endodermal resistance license expansion of the pericycle and how the topology of the endodermis influences the formation of the new root. These findings highlight the interconnected relationship between mechanics and auxin flow during lateral root initiation, emphasizing the vital role of the endodermis in shaping root development through mechanotransduction and auxin signaling.</p>","PeriodicalId":8922,"journal":{"name":"Biophysical journal","volume":" ","pages":"942-953"},"PeriodicalIF":3.2,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11947471/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141431200","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}
Biophysical journalPub Date : 2025-03-18Epub Date: 2025-02-14DOI: 10.1016/j.bpj.2025.02.012
Yathreb Easa, Olga Loza, Roie Cohen, David Sprinzak
{"title":"Fat4 intracellular domain controls internalization of Fat4/Dchs1 planar polarity membrane complexes.","authors":"Yathreb Easa, Olga Loza, Roie Cohen, David Sprinzak","doi":"10.1016/j.bpj.2025.02.012","DOIUrl":"10.1016/j.bpj.2025.02.012","url":null,"abstract":"<p><p>The Fat/Dachsous (Ft/Ds) pathway is a highly conserved pathway regulating planar cell polarity (PCP) across different animal species. Proteins from the Ft and Ds family are large transmembrane protocadherins that form heterophilic complexes on the boundaries between cells. Fat4 and Dchs1, the main mammalian homologs of this pathway, have been implicated in PCP in various epithelial tissues and were shown to form extremely stable complexes at the boundaries between cells. It is unclear, however, what are the dynamics controlling such stable boundary complexes, and how the formation and internalization of these complexes is regulated. Here, we use quantitative live imaging to elucidate the role of the intracellular domains (ICDs) of Fat4 and Dchs1 in regulating Fat4/Dchs1 complex dynamics. We show that removing the ICD of Fat4 results in a reduction of both trans-endocytosis of Dchs1 into the Fat4 cells and boundary accumulation of Fat4/Dchs1 complexes, but does not affect the diffusion of the complexes at the boundary. We further show that the ICD of Fat4 controls the internalization rate of Fat4/Dchs1 complexes. Finally, we find that while actin polymerization is required for the accumulation at the boundary of Fat4/Dchs1 complexes, we do not identify correlations between Fat4/Dchs1 complexes and local actin accumulation. Overall, we suggest that the Fat4 ICD is important for the internalization and plasticity of the highly stable Fat4/Dchs1 complexes associated with PCP.</p>","PeriodicalId":8922,"journal":{"name":"Biophysical journal","volume":" ","pages":"1024-1033"},"PeriodicalIF":3.2,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11947466/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143424930","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}
Biophysical journalPub Date : 2025-03-18Epub Date: 2025-03-12DOI: 10.1016/j.bpj.2025.02.011
Sham Tlili, Murat Shagirov, Shaobo Zhang, Timothy E Saunders
{"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}
Biophysical journalPub Date : 2025-03-18Epub Date: 2024-05-07DOI: 10.1016/j.bpj.2024.05.003
Carles Falcó, Daniel J Cohen, José A Carrillo, Ruth E Baker
{"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}
Biophysical journalPub Date : 2025-03-18Epub Date: 2024-03-26DOI: 10.1016/j.bpj.2024.03.028
Ludmilla de Plater, Julie Firmin, Jean-Léon Maître
{"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}
Biophysical journalPub Date : 2025-03-18Epub Date: 2024-08-20DOI: 10.1016/j.bpj.2024.08.011
Lili Zhang, Lydia Hodgins, Shariful Sakib, Alexander Verbeem, Ahmad Mahmood, Carmina Perez-Romero, Robert A Marmion, Nathalie Dostatni, Cécile Fradin
{"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}
Biophysical journalPub Date : 2025-03-18Epub Date: 2024-03-08DOI: 10.1016/j.bpj.2024.03.013
Shintaroh Kubo, Yasushi Okada
{"title":"The ATPase asymmetry: Novel computational insight into coupling diverse F<sub>O</sub> motors with tripartite F<sub>1</sub>.","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<sub>O</sub> motor, which presents variable symmetry, and a tripartite F<sub>1</sub> motor. Despite extensive research, the understanding of their coupling dynamics, especially with non-10-fold symmetrical F<sub>O</sub> motors, remains incomplete. This study investigates the coupling patterns between eightfold and ninefold F<sub>O</sub> motors and the constant threefold F<sub>1</sub> motor using coarse-grained molecular dynamics simulations. We unveil that in the case of a ninefold F<sub>O</sub> motor, a 3-3-3 motion is most likely to occur, whereas a 3-3-2 motion predominates with an eightfold F<sub>O</sub> motor. Furthermore, our findings propose a revised model for the coupling method, elucidating that the pathways' energy usage is primarily influenced by F<sub>1</sub> 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}
Biophysical journalPub Date : 2025-03-18Epub Date: 2024-06-19DOI: 10.1016/j.bpj.2024.06.016
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
{"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}
Biophysical journalPub Date : 2025-03-18Epub Date: 2024-12-04DOI: 10.1016/j.bpj.2024.12.003
Ian Seim, Stephan W Grill
{"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}