Physical biology最新文献

{"title":"Learning the mechanism of collective microbial function via random community-media pairing.","authors":"Luoqi Wang, Seppe Kuehn, Mikhail Tikhonov","doi":"10.1088/1478-3975/aeb3c4","DOIUrl":"https://doi.org/10.1088/1478-3975/aeb3c4","url":null,"abstract":"<p><p>In microbial systems, many biochemical functions arise from pathways encoded and executed at the community level. The collective nature of these functions complicates bottom-up efforts to determine each species' contribution. Previous work has shown that regression over randomly sampled datasets of collective functions succeeds at predicting those functions. Building on this top-down idea, this paper asks whether regression can also reveal mechanistic insight into a cross-feeding relationship. For this, we propose extending the random sampling method to vary the growth environment, cultivating each community in the spent medium of another randomly constructed community. Using a model-based analysis, we illustrate that the mechanistic roles of species are structurally non-identifiable under the standard random sampling protocol, but become identifiable after the proposed modification, such that even a simple LASSO regression can recover them. More generally, our work suggests that the utility of machine-learning-based approaches can be greatly enhanced by a synergistic experimental design.</p>","PeriodicalId":20207,"journal":{"name":"Physical biology","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149183882","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}

{"title":"Testing the Avrami-Dobrzyński model of cancer transformation using mutation-count clinical data across multiple tumour types.","authors":"Julianna Krasowska, Agata Fronczak, Piotr Fronczak, Joanna Reszczyńska, Sylwester Sommer, Krzysztof Wojciech Fornalski","doi":"10.1088/1478-3975/aeb3c2","DOIUrl":"https://doi.org/10.1088/1478-3975/aeb3c2","url":null,"abstract":"<p><strong>Background: </strong>The Avrami-Dobrzyński (A-D) model interprets malignant transformation as a phase-transition-like process, mathematically equivalent to the Johnson-Mehl-Avrami-Kolmogorov (JMAK) equation from condensed-matter physics.In this framework, the cumulative probability of neoplastic transformation follows a Weibull-type sigmoidal function of the somatic mutation burden, parametrised by a shape constant a and a critical scaling exponent k.&#xD;Purpose: To test the generalisability of the A-D model by fitting its cumulative distribution function to clinical mutation-count data spanning 24 cancer types, and to analyse meaning of its parameters across a heterogeneous patient population.&#xD;Methods: Mutation-count data for 70 studies (24 tumour types, n ≥ 100 per study) were retrieved from cBioPortal. For each cohort, an empirical cumulative distribution P(m) was constructed from total non-synonymous mutation counts per sample. One-, two-, and three-component A-D mixture models (equivalent to Weibull mixture distributions) were fitted.&#xD;Results: Single-component A-D fits adequately described a minority of cohorts; the majority exhibited a characteristic \"knee\" or wave-like inflection in the linearised representation, requiring two-or three-component mixture models. The scaling exponent k varied widely across and fell below unity in 37 of 136 fitted components, indicating a decreasing-hazard regime. The k-a parameter space showed systematic co-variation with mean mutation burden. Superposition of decreasing-and increasing-hazard components within individual tumour categories generated composite hazard profiles, reflecting coexisting subpopulations with distinct transformation dynamics.&#xD;Conclusions:The A-D model provides a physically grounded description of mutation-driven cancer transformation across diverse tumour types. Deviations from single-component behaviour are consistent with genuine biological heterogeneity within nominal tumour categories. These findings support the broader applicability of phase-transition concepts in computational oncology and provide a quantitative framework for integrating genomic data into cancer risk modelling.</p>","PeriodicalId":20207,"journal":{"name":"Physical biology","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149183902","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}

{"title":"Decoupling Bulk Stiffness and Pore Size in 3D Rat Tail Collagen I Matrices.","authors":"Theadora Vessella, Qi Wen, H Susan Zhou","doi":"10.1088/1478-3975/aeb3c3","DOIUrl":"https://doi.org/10.1088/1478-3975/aeb3c3","url":null,"abstract":"<p><p>The interplay between extracellular matrix (ECM) mechanics and the tumor microenvironment is increasingly recognized as a key driver of cancer progression. Three-dimensional (3D) collagen I culture systems provide more physiologically relevant environments than traditional 2D cultures, yet seperately controlling the structural and mechanical features of 3D matrices remains challenging due to their inherent interdependence. Here, we present a collagen-based approach to decouple bulk stiffness and pore size by varying collagen concentration and polymerization temperature. Collagen concentration was varied to modulate bulk storage modulus, while polymerization temperature was adjusted to alter pore dimensons at comparable collagen concentrations. Using this approach, we generated 3D Collagen I matrices with bulk storage moduli of approximately 80, 228, and 360 Pa while maintaining a similar median pore sizes near 2.5 µm. Conversely, 1.5 mg/mL collagen, median pore size varied from approximately 2.5 to 3.1 µm while bulk storage modulus ramined near 80 Pa, whereas at 3.5 mg/mL collagen, pore size varied from approximately 2.0 to 2.4 µm while bulk storage modulus remained near 350 Pa. We further evaluated the responses of MCF-10A epithelial cells and MDA-MB-231 metastatic breast cancer cells to matrices spanning these sturactual and mechanical conditions. Although the changes in pore size within each stiffness range were modest, they were associated with measurable and statistical differences in cell morphology. These findings demonstrate that even modest changes in collagen network architecture can produce measurable differences in cellular behvarior under comparable bulk mechanical conditions, highlighitng the importance of considering matrix structure in addition to stiffness when investigating cell-matrix interactions.</p>","PeriodicalId":20207,"journal":{"name":"Physical biology","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149183819","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}

{"title":"Spanning-tree thermostatistics of protein allostery: an exact Kirchhoff framework with application to oncogenic KRAS.","authors":"Fatma Senguler Ciftci, Burak Erman","doi":"10.1088/1478-3975/ae9e79","DOIUrl":"10.1088/1478-3975/ae9e79","url":null,"abstract":"<p><p>This study introduces a statistical mechanical framework for allosteric communication in proteins based on the spanning-tree ensemble of residue contact networks. By representingprotein backbones as weighted graphs, we identify each spanning tree as a topological microstate. The canonical partition function is evaluated analytically via the determinant of the reduced weighted Kirchhoff (Laplacian) matrix, allowing for the derivation of global thermodynamic functions (including Helmholtz free energy, internal energy, entropy, and heat capacity) without stochastic sampling. Allosteric channels between specific residue pairs are defined as sub-ensembles containing unique simple paths. Using the Burton-Pemantle theorem and the Moore-Penrose pseudoinverse of the graph Laplacian, we compute path probabilities and channel-specific thermodynamics. This methodology enables a decomposition of channel heat capacity into energetic and topological components and quantifies residue-level allosteric importance through fractional contributions to the channel partition function. The framework was applied to the G12D mutation in KRAS, comparing wild-type (PDB: 6GOD) and mutant (PDB: 6GOF) structures. Results show that while global thermodynamic properties remain highly conserved across the tight structural superposition, channel-level analysis shows a substantial internal redistribution of allosteric importance among intermediate residues, highlighted by the primary 12-61 signaling axis and distal routes (including shifts in residues such as Q61 and F156). Operating onbackbone geometry, these topological shifts provide predictive hypotheses for subsequent molecular dynamics and experimental testing. Overall, this approach offers a rigorous, parameter-robust framework for understanding how point mutations perturb distal signaling networks.</p>","PeriodicalId":20207,"journal":{"name":"Physical biology","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2026-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148819388","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}

{"title":"Proton flows, proton gradients and subcellular architecture in biological energy conversion.","authors":"Luca Quaroni","doi":"10.1088/1478-3975/ae9664","DOIUrl":"10.1088/1478-3975/ae9664","url":null,"abstract":"<p><p>Hydrogen cations, or protons, provide a medium by which energy is stored in biological systems and converted for use in metabolic transformations. Such pre-eminence relies on the interplay between interfacial and bulk or chemical transformations, according to mechanisms that are shared by organisms in all phyla of life. The present work describes the fundamental aspects of biological energy management by focusing on the relationship between vectorial proton flows and the geometry of energy producing organelles in eukaryotes. The two leading models of proton-mediated energy conversion, the delocalised proton (or chemiosmotic) model and the localised proton model, are presented in a complementary perspective. While the delocalised model provides a description that relies on equilibrium thermodynamics, the localised model addresses dynamic processes that are better described using out-of-equilibrium thermodynamics. The work reviews the salient aspects of such mechanisms, traces the development of our present understanding, and highlights the areas that are open to future developments.</p>","PeriodicalId":20207,"journal":{"name":"Physical biology","volume":"23 5","pages":""},"PeriodicalIF":1.5,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148881512","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}

{"title":"Steady-state thermal homeostasis model of heat generated and dissipated in the human retina.","authors":"Christina Kiel, Alexander J E Foss","doi":"10.1088/1478-3975/ae9665","DOIUrl":"10.1088/1478-3975/ae9665","url":null,"abstract":"<p><p>The retina is both metabolically active and exposed to light, resulting in persistent heat generation. However, the quantitative contributions of metabolic and irradiative heat sources, and the mechanisms responsible for dissipating this thermal load, remain incompletely characterized. Here we develop a steady-state quantitative thermal balance model of the retina that integrates heat production from metabolic activity and light absorption with multiple heat dissipation pathways into a unified energy balance framework. Metabolic heat was estimated from reported ATP consumption rates under dark-and light-adapted conditions, while irradiative heat input was quantified based on environmental luminance, pupil size, and ocular optics. These inputs were incorporated into a lumped energy balance in the form of, allowing calculation of the retinal temperature elevation relative to blood,. Heat dissipation pathways, including conduction to surrounding tissue, choroidal blood perfusion, convection, and radiation, were expressed as thermal conductances,and analyzed within the same framework,. Under sunlight, total retinal heat input reached approximately 10 mW, approximately threefold higher than at night. Despite this, the predicted steady-state retinal temperature elevation remained very small (∼10^-3K), suggesting that heat is dissipated highly efficiently. The analysis shows that conduction and choroidal blood perfusion dominate retinal heat removal under physiological conditions, whereas radiation and convection contribute negligibly. The results suggest that retinal heat redistribution via conduction plays a major role in retinal thermal homeostasis, whereas choroidal blood perfusion primarily contributes to subsequent systemic heat removal rather than acting as a dominant limiting mechanism itself. This analysis provides quantitative support for the long-standing hypothesis that the choroid functions as a heat sink for the retina.</p>","PeriodicalId":20207,"journal":{"name":"Physical biology","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2026-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148685454","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}

{"title":"Nonequilibrium temperature fluctuations as modulators of mitochondrial elastocapillary stability.","authors":"Peyman Fahimi","doi":"10.1088/1478-3975/ae934f","DOIUrl":"https://doi.org/10.1088/1478-3975/ae934f","url":null,"abstract":"<p><p>Recent studies have suggested that under high or near-maximal mitochondrial respiratory activity, ion-translocating proteins within the inner mitochondrial membrane may generate transient nonequilibrium temperature fluctuations in the adjacent mitochondrial matrix and intermembrane space. Such nonequilibrium temperature fluctuations may, in principle, influence mitochondrial mechanics and morphology. Building on elastocapillary models of mitochondrial dynamics, we investigate whether these nonequilibrium temperature fluctuations can modulate the stability of mitochondrial tubules through temperature-dependent changes in effective membrane tension and elasticity. Our numerical analysis predicts that this effect is strongly threshold-dependent: in deeply unstable states, thermal modulation remains insufficient to restore stability, whereas closer to the threshold, temperature-dependent reduction of effective membrane tension can overcome temperature-dependent elastic softening, thereby increasing the elastocapillary number, suppressing unstable modes, and shifting mitochondria toward mechanically more stable tubular states. In other words, when mitochondria begin shifting toward fission-promoting states, elevated respiratory activity, which increases the magnitude and cumulative temporal occupancy of transient thermal perturbations, tends to shift the system back toward mechanical stability. However, when mitochondria are already far within the mechanically unstable regime, transient thermal activity is no longer sufficient to restore stability. This stabilizing regime is qualitatively consistent with experimental observations linking elevated oxidative phosphorylation to mitochondrial elongation, fusion, or hyperfusion rather than fragmentation.</p>","PeriodicalId":20207,"journal":{"name":"Physical biology","volume":"23 4","pages":""},"PeriodicalIF":1.5,"publicationDate":"2026-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148766590","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}

{"title":"Dynamical modeling and bifurcation analysis of malaria transmission under synergistic control of Wolbachia-infected male release and chemical insecticides.","authors":"Xinyu Wang, Wei Zhou, Liping Wang","doi":"10.1088/1478-3975/ae8aa7","DOIUrl":"10.1088/1478-3975/ae8aa7","url":null,"abstract":"<p><p>In this article, we integrate the release of Wolbachia-carrying male mosquitoes with chemical insecticide spraying to formulate a coupled model that incorporates mosquito stage structure and malaria transmission dynamics. The model accounts for mating competition influenced by cytoplasmic incompatibility and employs a Holling-II type saturated release mechanism to dynamically match the release intensity of infected male mosquitoes with the density of wild mosquitoes. The study first verifies the positive invariance and boundedness of solutions of the model. It then derives the basic reproduction number, followed by the existence conditions and stability properties of equilibria. Subsequently, it reveals saddle-node bifurcation, forward bifurcation, backward bifurcation and their compound phenomena, thereby elucidating the abrupt dynamic changes near parameter thresholds of the system. Numerical simulations validate the theoretical results, quantify the regulatory effects of key parameters, and confirm that the combined strategy effectively suppresses mosquito population growth and interrupts malaria transmission through synergistic effects. The results illustrate that accurate tuning of critical parameters for the integrated control strategy and exploitation of synergism between Wolbachia and chemical insecticides can effectively modulate mosquito populations and block malaria transmission.</p>","PeriodicalId":20207,"journal":{"name":"Physical biology","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2026-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148448739","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}

{"title":"Effect of high mobility group box-1 on receptor for advanced glycation endproducts (RAGE) and toll-like receptor-4 (TLR4) diffusion and signaling.","authors":"Sharifur Rahman, Chamari S Wijesooriya, Gennady V Pogorelko, Mohammad K I Walid, Pegah Roshandel, Marit Nilsen-Hamilton, Emily A Smith","doi":"10.1088/1478-3975/ae9030","DOIUrl":"10.1088/1478-3975/ae9030","url":null,"abstract":"<p><p>High mobility group box-1 (HMGB1) is a damage-associated molecular pattern and a ligand for multiple immune receptors, including receptors for advanced glycation endproducts (RAGE) and toll-like receptor 4 (TLR4). Binding of HMGB1 to these receptors initiates inflammatory signaling cascades implicated in diseases such as septic shock, chronic inflammation, and autoimmune disorders. The spatial and molecular mechanisms underlying HMGB1-mediated receptor signaling at the plasma membrane remain poorly understood. Here, single-particle tracking was used to investigate the effects of extracellular HMGB1 on RAGE's and TLR4's diffusion properties in human embryonic kidney 293 (HEK293) cells. HMGB1 treatment reduced the Brownian diffusion coefficients by 27% and 24% for RAGE (with and without TLR4 co-expression, respectively) and by 40% and 21% for TLR4 (with and without RAGE co-expression, respectively). HMGB1 treatment reduced the size of the confined domains the receptors diffuse into and increased the number of times the two receptors came in close proximity. In contrast, HMGB1 had no detectable effect on the diffusion properties of an S391A RAGE mutant, which lacks the ability to recruit adapter proteins. Lipid diffusion measurements revealed that HMGB1 treatment decreases lipid membrane fluidity in all cell lines studied. Similarly, phalloidin staining revealed no detectable HMGB1-induced changes in actin organization in RAGE expressing cells. Functionally, HMGB1 treatment activated the extracellular signal-regulated kinase (ERK) (1/2) signaling pathway through both RAGE and TLR4, whereas ERK (1/2) and p38 MAPK activation by HMGB1 were abolished in cells expressing S391A RAGE. Together, these findings show that HMGB1 reduced confined receptor diffusion and increased nanoscale proximity while promoting MAPK signaling. This work sheds new light on the nanoscale regulation of innate immune receptors by HMGB1 and emphasizes membrane biophysics as one critical component of inflammatory signaling outcomes.</p>","PeriodicalId":20207,"journal":{"name":"Physical biology","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2026-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148585073","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}

{"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}