{"title":"Scaling of the Bicoid morphogen gradient: the effect of state dependent diffusion.","authors":"Priya Chakraborty, Shyam Iyer, Richa Rikhy, Mithun K Mitra, Amitabha Nandi","doi":"10.1088/1478-3975/ae9031","DOIUrl":"10.1088/1478-3975/ae9031","url":null,"abstract":"<p><p>The mechanisms underlying the scaling of the Bicoid morphogen gradient in Drosophila with the embryo size is not clearly understood. We propose a model with a spatially varying diffusion coefficient along the anterior-posterior axis, that is proportional to the nearly periodic spatial distribution of the nucleo-cytoplasmic domains and alternating between regions of fast and slow diffusion. We postulate that for specific interpretation of the heterogeneous environment, where the space available for free diffusion within an energid is assumed to be proportional to the embryo size, a change in the embryo size can lead to a size-dependent scaling of the gradient lengthscale. We further study a two component model with slow and fast diffusing Bicoid, and identify this model to be equivalent to the heterogeneous diffusion model further postulating that the<i>fast-state occupancy</i>which is a measure of the fraction of time spent in the fast diffusing state, should also scale with the embryo size via the energid size. Finally, we incorporate nuclear shuttling into our model to understand the effect of shuttling on the gradient lengthscale and scaling with embryo size. We argue that for the particular case where the degradation within the nucleus is low, nuclear shuttling does not perturb the Bicoid gradient. Our study suggests that spatial heterogeneity is able to generate scaling, independent of nuclear trapping. This mechanism may act in conjunction with other biological processes, to yield the experimentally observed scaling behavior of the Bicoid gradient.</p>","PeriodicalId":20207,"journal":{"name":"Physical biology","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2026-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148585099","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}
Physical biologyPub Date : 2026-08-07DOI: 10.1088/1478-3975/ae8fb0
Thomas Perros, Stéphane Joly, Adama Mbaye, Philippe Marcq, Olivier Cochet-Escartin
{"title":"Wnt signaling modulates tissue mechanics, actin order, and regeneration in<i>Hydra vulgaris</i>.","authors":"Thomas Perros, Stéphane Joly, Adama Mbaye, Philippe Marcq, Olivier Cochet-Escartin","doi":"10.1088/1478-3975/ae8fb0","DOIUrl":"10.1088/1478-3975/ae8fb0","url":null,"abstract":"<p><p><i>Hydra vulgaris</i>is a powerful model organism in the study of axial patterning and regeneration. While recent models emphasize the importance of mechanical cues in establishing the body axis of<i>Hydra</i>tissue spheres, the precise role of the Wnt pathway, known to be central to axial patterning, in regulating tissue mechanics and cytoskeletal organization remains unclear. In this paper, we pharmacologically modulated the canonical Wnt pathway using alsterpaullone (AP) and iCRT14 and assessed their effects on regeneration, tissue rheology, osmotic oscillations and actin organization in<i>Hydra</i>tissue spheres. We found that AP prevents full regeneration, softens the constitutive tissues, disrupts osmotic oscillations and increases the area coverage of oriented actin fibers. Conversely, we found that treatment with iCRT14 does not systematically block regeneration despite inducing a small decrease in actin fibers area coverage. These results support the underlying hypotheses of two existing mechano-chemical models of<i>Hydra</i>patterning, suggesting that Wnt-driven feedbacks on both tissue stiffness and actin order could contribute to the robust emergence of body axes. Our findings highlight the possibility of redundant and coupled mechanisms in the<i>Hydra</i>patterning system, potentially explaining its robustness.</p>","PeriodicalId":20207,"journal":{"name":"Physical biology","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2026-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148579949","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}
Physical biologyPub Date : 2026-07-31DOI: 10.1088/1478-3975/ae8d70
Ysaías J Alvarado, Arlene Cardozo-Urdaneta, Alejandro Vivas, Carla Lossada, Aníbal Mendez, Edgar Portillo, María Elena Troconis, Ariana Delgado, Yasmir Quiroz, Marylu Mora, Yovani Marrero-Ponce, Félix Martinez-Rios, Yunierkis Pérez-Castillo, Joan Vera-Villalobos, Julio de la Paz, Lenin González-Paz
{"title":"A cross-scale physical framework for transcription-associated CPEB4 microexon susceptibility and crowding-enhanced isoform self-association: toward a biophysical mechanism of idiopathic autism.","authors":"Ysaías J Alvarado, Arlene Cardozo-Urdaneta, Alejandro Vivas, Carla Lossada, Aníbal Mendez, Edgar Portillo, María Elena Troconis, Ariana Delgado, Yasmir Quiroz, Marylu Mora, Yovani Marrero-Ponce, Félix Martinez-Rios, Yunierkis Pérez-Castillo, Joan Vera-Villalobos, Julio de la Paz, Lenin González-Paz","doi":"10.1088/1478-3975/ae8d70","DOIUrl":"10.1088/1478-3975/ae8d70","url":null,"abstract":"<p><p>Co-transcriptional splicing and protein self-assembly are governed by coupled kinetic and thermodynamic constraints, such that modest changes in exon processing can propagate into substantial shifts in isoform-dependent mesoscale behavior. Here, we develop a cross-scale physical framework to examine whether transcription-associated kinetic pressure could differentially bias CPEB4 microexon selection and thereby reshape downstream isoform behavior. Using a simplified transcriptional kinetic model, we define an acetylation-associated high-throughput regime as a coarse-grained proxy for reduced time available for co-transcriptional exon recognition. Comparative sequence and structural analyses identify microexon 4 (me4) as less robust than microexon 3 (me3), with weaker cis-regulatory support and lower thermodynamic stability, consistent with greater susceptibility to omission under kinetically constrained conditions. A reduced probabilistic splicing framework accordingly predicts a directional bias against me4, superimposed on a basal transcript landscape in which the full-length isoform remains present. As a complementary downstream analysis, scaled-particle-theory calculations indicate that representative Δ4-enriched scenarios thermodynamically favor homotypic self-association under macromolecular crowding, suggesting a plausible physical amplification route for modest splicing bias. Orthogonal measurements in a yeast perturbation system identify oxidative and spectroscopic signatures compatible with strong butyrate-associated physicochemical stress, but these are interpreted as perturbation readouts rather than direct measurements of neuronal histone acetylation or splicing. Together, these results define a testable cross-scale framework linking transcription-associated kinetic constraints, directional microexon susceptibility, and crowding-dependent remodeling of the CPEB4 isoform assembly landscape.</p>","PeriodicalId":20207,"journal":{"name":"Physical biology","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2026-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148536782","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}
Physical biologyPub Date : 2026-07-31DOI: 10.1088/1478-3975/ae8d71
Hiba Khan, Paula Garcia-Galindo, Sebastian Ahnert, Kamal Dingle
{"title":"Comparing random and natural RNA Boltzmann ensembles.","authors":"Hiba Khan, Paula Garcia-Galindo, Sebastian Ahnert, Kamal Dingle","doi":"10.1088/1478-3975/ae8d71","DOIUrl":"10.1088/1478-3975/ae8d71","url":null,"abstract":"<p><p>A<i>morphospace</i>is an abstract space of theoretically possible biological traits, shapes, or property values. It is interesting to explore which parts of a morphospace life occupies, as compared to those parts which could be occupied, but are not. Comparing random and natural non-coding (nc) RNA secondary structures is an established approach to studying morphospace occupation for RNA structures. Most earlier studies have focused on the minimum free energy structure, while relatively few have looked at the Boltzmann distribution, describing the ensemble of energetically suboptimal RNA folds. These suboptimal structures may have important roles and functions, and hence should be examined carefully. Here we compare random and natural ncRNA in terms of their Boltzmann distributions, finding that natural RNA tend to have very similar profiles to random RNA, with the main difference being that natural RNA are slightly more energetically stable, except for very short sequences (20 to 30 nucleotides) which appear to be equally or slightly<i>less</i>stable. We infer that natural ncRNA and random RNA occupy similar parts of the morphospace, indicating that the biophysics of the genotype-phenotype map largely determines the ensemble properties of ncRNA.</p>","PeriodicalId":20207,"journal":{"name":"Physical biology","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2026-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148536756","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}
Physical biologyPub Date : 2026-06-25DOI: 10.1088/1478-3975/ae7ad6
Christina Kiel, Stella Prins, Alexander J E Foss
{"title":"Quantitative models of photoreceptor metabolisms: implications for rod outer segment length, retinal glycolysis and choroidal blood flow.","authors":"Christina Kiel, Stella Prins, Alexander J E Foss","doi":"10.1088/1478-3975/ae7ad6","DOIUrl":"10.1088/1478-3975/ae7ad6","url":null,"abstract":"<p><p>The outer retina exhibits several distinctive physiological features, including continuous turnover of rod photoreceptor outer segments (OS), a strong reliance on aerobic glycolysis despite oxygen availability, and an unusually high rate of choroidal blood flow. The mechanistic links between these phenomena remain incompletely understood. Here, we present a quantitative reaction-diffusion model of energy metabolism in rod photoreceptors that connects metabolic supply and demand to OS length and daily shedding. Because rod OS lack mitochondria, ATP and glycolytic intermediates must be supplied by diffusion from the inner segment, where oxidative phosphorylation and the initial steps of glycolysis occur. We model the diffusion and consumption of ATP and fructose-1,6-bisphosphate along the OS and show that diffusion-limited energy supply constrains OS length. Using literature-derived parameters, the model accurately predicts observed OS lengths in mammals (∼28<i>µ</i>m) and amphibians (∼50<i>µ</i>m), explains diurnal variations in OS length and tip shedding at light onset, and provides a unified explanation for the coexistence of high glycolytic flux, low oxygen extraction, and high choroidal blood flow in the outer retina. The model generates experimentally testable predictions regarding metabolite gradients along the OS and offers a general framework for understanding how metabolic constraints shape cellular morphology and tissue-level physiology.</p>","PeriodicalId":20207,"journal":{"name":"Physical biology","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2026-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148212361","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}
Physical biologyPub Date : 2026-06-09DOI: 10.1088/1478-3975/ae6c84
Vaibhav Anand, Mohit Kumar Jolly, Herbert Levine
{"title":"Ecological dynamics of pro-tumor and anti-tumor teams in the tumor microenvironment.","authors":"Vaibhav Anand, Mohit Kumar Jolly, Herbert Levine","doi":"10.1088/1478-3975/ae6c84","DOIUrl":"10.1088/1478-3975/ae6c84","url":null,"abstract":"<p><p>Tumor growth occurs within a complex tumor microenvironment (TME) composed of many interacting cell types. However, the signs of tumor-immune interactions in this ecosystem are not random and possess a structure, the immune cell types in the TME tend to organize into two functional communities: a pro-tumor team and an anti-tumor team, each internally cooperative but mutually antagonistic, forming a two-team ecosystem. Quantitatively predicting the ecological outcomes of such interactions remains challenging due to cellular diversity and interaction variability, and the exact dynamical regimes accessible to such a two-team ecosystem remain unknown. Here, we model tumor-immune interactions as a structured ecosystem with two competing teams using a generalized Lotka-Volterra framework and analyze it using the cavity method. We derive phase diagrams that delineate when these two communities coexist, when one dominates, and how these outcomes depend on intra-team cooperation, cross-team inhibition, and ecological heterogeneity. Our work provides a foundation for understanding tumor-immune dynamics from a community ecology perspective.</p>","PeriodicalId":20207,"journal":{"name":"Physical biology","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2026-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147932622","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}
Physical biologyPub Date : 2026-06-04DOI: 10.1088/1478-3975/ae7247
Samaneh Rahbar, Ludger Santen, Reza Shaebani
{"title":"Mechanical interactions govern self-organized ordering in bacterial colonies on surfaces.","authors":"Samaneh Rahbar, Ludger Santen, Reza Shaebani","doi":"10.1088/1478-3975/ae7247","DOIUrl":"10.1088/1478-3975/ae7247","url":null,"abstract":"<p><p>Bacterial colonies growing on surfaces are shaped by mechanical stresses transmitted through the community, governed by the balance between cell growth and steric and cell-substrate interactions. Using overdamped dynamics simulations of nonmotile, stress-responsive bacteria, we systematically investigate how these mechanical factors determine colony morphology and internal organization. Growth-induced extensile stresses compete with steric constraints, giving rise to the spontaneous formation of microdomains composed of highly aligned cells. We characterize this self-organization through the distribution of microdomain areas and a nematic order parameter that quantifies colony-wide alignment. We find that substrate friction plays a key role in controlling domain size and orientational diversity, whereas mechanosensitive growth, despite introducing a feedback between stress and proliferation, does not systematically alter domain structure within the biologically relevant regime. Increasing the division length enhances steric effects, slows the relaxation of colony shape toward isotropy, and broadens the distribution of contact forces. In dense colonies, strong forces are transmitted anisotropically through chains of aligned neighbors within microdomains. These results demonstrate that colony-level morphology and stress organization can emerge from local mechanical interactions alone. More broadly, our study establishes how substrate interactions, proliferation dynamics, and stress-growth coupling jointly govern the self-organization of bacterial communities under surface confinement.</p>","PeriodicalId":20207,"journal":{"name":"Physical biology","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2026-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148006375","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}
Physical biologyPub Date : 2026-05-28DOI: 10.1088/1478-3975/ae6e88
Robert G Endres
{"title":"Robust chemotaxis beyond sensing limits: signal, noise, and strategy.","authors":"Robert G Endres","doi":"10.1088/1478-3975/ae6e88","DOIUrl":"10.1088/1478-3975/ae6e88","url":null,"abstract":"<p><p>Bacterial chemotaxis has long been viewed as operating near the physical limits of sensing, as originally articulated by Berg and Purcell. Recent information-theoretic analyses challenge this view, suggesting that<i>Escherichia coli</i>uses only a small fraction of the information available in ligand arrival statistics to bias its motion. How should such low information efficiency be interpreted at the level of behavior? Here, I argue that chemotactic performance is shaped not only by information transmission and noise, but by the strategy of movement itself. Using simple scaling arguments and minimal models, I show how run-and-tumble chemotaxis can remain robust to noise through symmetry and temporal averaging, even when internal information processing is inefficient. Comparing bacterial and eukaryotic chemotaxis highlights how different sensing strategies convert physical limits into observable behavior. These considerations suggest that low information efficiency need not imply poor performance, but may instead reflect an evolved balance between robustness, simplicity, and function.</p>","PeriodicalId":20207,"journal":{"name":"Physical biology","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2026-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147948696","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}
Physical biologyPub Date : 2026-05-20DOI: 10.1088/1478-3975/ae6af1
Andy M Reynolds
{"title":"Swarms of female<i>Anopheles gambiae</i>mosquitoes may fracture when perturbed.","authors":"Andy M Reynolds","doi":"10.1088/1478-3975/ae6af1","DOIUrl":"10.1088/1478-3975/ae6af1","url":null,"abstract":"<p><p>In contrast with bird flocks, schools of fish, and migratory herds that display directed motion, mating swarms of male insects do not possess global order. Over the last decade or so, substantial progress has been made in quantitatively demonstrating the collective nature of these swarms. Their emergent collective behaviour cannot be determined by passive observations alone; instead, they must be perturbed. Here I identify a new putative emergent property of swarming by modelling the first detailed experimental studies of swarms of female insects. I show that swarms of female<i>Anopheles gambiae</i>mosquitoes are predicted to undergo cohesion-to-fragmentation (order-to-disorder) transitions and so are prone to disintegration in the face of environmental perturbations. This may explain why it is difficult, if not impossible, to observe pure female swarms of<i>Anopheles</i>mosquitoes in the wild. More generally, the new results may explain why most natural swarms of insects fit into one of two classes, namely uniformly distributed and clumped, which are the extremes of a continuum.</p>","PeriodicalId":20207,"journal":{"name":"Physical biology","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2026-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147856650","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}
Physical biologyPub Date : 2026-05-11DOI: 10.1088/1478-3975/ae65f8
Mary L DorChhuon, T Bagarti, Niraj Kumar
{"title":"How exercise scheduling affects IL-6-mediated tumor suppression: a fixed exercise volume perspective.","authors":"Mary L DorChhuon, T Bagarti, Niraj Kumar","doi":"10.1088/1478-3975/ae65f8","DOIUrl":"10.1088/1478-3975/ae65f8","url":null,"abstract":"<p><p>Recent investigations into exercise-induced tumor suppression suggest that higher exercise frequency enhances tumor control when the total duration of exercise within a specified time window is not constrained. An equally compelling avenue for exploration is the effect of increased exercise frequency under the condition of a fixed total exercise duration within the same time frame. Using a mathematical model of IL-6-mediated interactions between natural killer cells and tumor cells, here we explore how different combinations of exercise and rest intervals-while maintaining a constant overall exercise volume-affect tumor suppression. Our results reveal a nonmonotonic tumor response and key metrics such as the time of maximum tumor suppression and the duration of tumor suppression are found to decrease with increasing exercise frequency. Interestingly, unlike earlier study where increasing exercise frequency leads to increase in tumor suppression, here we find that under fixed exercise volume constraints, increased frequency diminishes therapeutic efficacy of exercise, suggesting exercise bouts with longer duration are more effective in suppressing tumors. These findings highlight the importance of considering total exercise volume when designing exercise-based cancer interventions.</p>","PeriodicalId":20207,"journal":{"name":"Physical biology","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2026-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147779032","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}