Biophysical journal最新文献

{"title":"Receptor binding and tortuosity explain morphogen local-to-global diffusion coefficient transition.","authors":"Shiwen Zhu, Yi Ting Loo, Sapthaswaran Veerapathiran, Tricia Y J Loo, Bich Ngoc Tran, Cathleen Teh, Jun Zhong, Paul Matsudaira, Timothy E Saunders, Thorsten Wohland","doi":"10.1016/j.bpj.2024.07.024","DOIUrl":"10.1016/j.bpj.2024.07.024","url":null,"abstract":"<p><p>Morphogens are intercellular signaling molecules providing spatial information to cells in developing tissues to coordinate cell fate decisions. The spatial information is encoded within long-ranged concentration gradients of the morphogen. Direct measurement of morphogen dynamics in a range of systems suggests that local and global diffusion coefficients can differ by orders of magnitude. Further, local diffusivity can be large, which would potentially abolish any concentration gradient rapidly. Such observations have led to alternative transport models being proposed, including transcytosis and cytonemes. Here, we show that accounting for tissue architecture combined with receptor binding is sufficient to hinder the diffusive dynamics of morphogens, leading to an order of magnitude decrease in the effective diffusion coefficient from local to global scales. In particular, we built a realistic in silico architecture of the extracellular spaces of the zebrafish brain using light and electron microscopy data. Simulations on realistic architectures demonstrate that tortuosity and receptor binding within these spaces are sufficient to reproduce experimentally measured morphogen dynamics. Importantly, this work demonstrates that hindered diffusion is a viable mechanism for gradient formation, without requiring additional regulatory control.</p>","PeriodicalId":8922,"journal":{"name":"Biophysical journal","volume":" ","pages":"963-979"},"PeriodicalIF":3.2,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141756971","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cell-to-cell signaling in cell populations with large cell size variability.","authors":"Yukihisa Hayashida, Chikoo Oosawa, Takuo Yasunaga, Yusuke V Morimoto","doi":"10.1016/j.bpj.2024.07.017","DOIUrl":"10.1016/j.bpj.2024.07.017","url":null,"abstract":"<p><p>Sizes of multiple cells vary when they communicate with each other. Differences in cell size result in variations in the cell surface area and volume, as well as the number of enzymes and receptors involved in signal transduction. Although heterogeneity in cell size may inhibit uniformity in signaling, cell-to-cell signaling is still possible. The outcome when cell size changes to an extreme degree remains unclear. Hence, we inhibited cell division in Dictyostelium cells, a model organism for signal transduction, to gain insights into the consequences of extreme cell size variations. Measurements of cell signals in this population using fluorescence microscopy indicated that the giant cells can communicate with normal-sized cells by suppressing the signal level. Simulations of signal transduction based on the FitzHugh-Nagumo model also suggested similar results. Our findings suggest that signaling mechanism homogenizes cell-to-cell signaling in response to cell size.</p>","PeriodicalId":8922,"journal":{"name":"Biophysical journal","volume":" ","pages":"954-962"},"PeriodicalIF":3.2,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141975033","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Membrane extraction in native lipid nanodiscs reveals dynamic regulation of Cdc42 complexes during cell polarization.","authors":"Lars N Deutz, Sena Sarıkaya, Daniel J Dickinson","doi":"10.1016/j.bpj.2023.11.021","DOIUrl":"10.1016/j.bpj.2023.11.021","url":null,"abstract":"<p><p>Embryonic development requires the establishment of cell polarity to enable cell fate segregation and tissue morphogenesis. This process is regulated by Par complex proteins, which partition into polarized membrane domains and direct downstream polarized cell behaviors. The kinase aPKC (along with its cofactor Par6) is a key member of this network and can be recruited to the plasma membrane by either the small GTPase Cdc42 or the scaffolding protein Par3. Although in vitro interactions among these proteins are well established, much is still unknown about the complexes they form during development. Here, to enable the study of membrane-associated complexes ex vivo, we used a maleic acid copolymer to rapidly isolate membrane proteins from single C. elegans zygotes into lipid nanodiscs. We show that native lipid nanodisc formation enables detection of endogenous complexes involving Cdc42, which are undetectable when cells are lysed in detergent. We found that Cdc42 interacts more strongly with aPKC/Par6 during polarity maintenance than polarity establishment, two developmental stages that are separated by only a few minutes. We further show that Cdc42 and Par3 do not bind aPKC/Par6 simultaneously, confirming recent in vitro findings in an ex vivo context. Our findings establish a new tool for studying membrane-associated signaling complexes and reveal an unexpected mode of polarity regulation via Cdc42.</p>","PeriodicalId":8922,"journal":{"name":"Biophysical journal","volume":" ","pages":"876-890"},"PeriodicalIF":3.2,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138433153","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"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":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"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":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"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":"","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":"","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":"","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":"","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":"","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":"","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":"","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":"","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":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}