Biophysical journal最新文献

{"title":"Hypoxia-responsive HIF-1α-dependent RhoA signaling promotes motility and aerotaxis in polyaneuploid PC3 cancer cells with increased nuclear rounding.","authors":"Noreen Hosny, Shengkai Li, Robert A Gatenby, Kenneth J Pienta, Joel S Brown, Emma U Hammarlund, Yu Chen, Junle Qu, Robert H Austin, Sarah R Amend","doi":"10.1016/j.bpj.2026.09.001","DOIUrl":"10.1016/j.bpj.2026.09.001","url":null,"abstract":"<p><p>Most cancer deaths result from metastasis, yet only a subset of tumor cells can complete this process. Polyaneuploid cancer cells (PACCs), which arise via endoreplication under stressors such as hypoxia, are implicated as metastatic drivers, but how they acquire this capacity remains unclear. Here, we show that under extreme self-generated hypoxia, the polyaneuploid subset of PC3 prostate cancer cells upregulates a hypoxia-responsive, HIF-1α-dependent RhoA signaling axis that promotes aerotaxis, a behavior predictive of intravasation during metastasis. We observe an enrichment of PACCs using a membrane-based culture system in which extreme, self-generated radial oxygen gradients emerge as cellular oxygen demand exceeds supply, recapitulating key features of the tumor microenvironment. Under these conditions, PACCs exhibited elevated HIF-1α and RhoA expression relative to non-PACCs. Disruption of either HIF-1α or RhoA attenuates aerotaxis, with RhoA expression suppressed upon HIF-1α inhibition, suggesting a functional HIF-1α-dependent RhoA pathway selectively enhanced in the PACC state. Quantitative analysis of nuclear morphology further reveals that nuclear circularity and solidity, morphology metrics associated with nuclear rounding and boundary organization, increase with and saturate at high nuclear area. Notably, the hypoxic PACC population exhibits significantly greater nuclear circularity and solidity compared with non-PACCs, suggesting increased rounding and stabilization of the enlarged nuclear architecture characteristic of PACCs under extreme hypoxia. Together, these findings reveal a new functional role for HIF-1α-dependent RhoA signaling in regulating aerotaxis in PACCs, which may enable aerotactic escape from hypoxic tumor cores and entry into oxygen-rich vasculature. Additionally, the association between elevated RhoA signaling and increased nuclear circularity at larger nuclear area suggests a potential link between hypoxia-responsive migration and maintenance of enlarged nuclear architecture in the PACC state. Collectively, these characteristics highlight PACCs as a hypoxia-adapted subpopulation with relevance for anti-metastatic therapeutic strategies.</p>","PeriodicalId":8922,"journal":{"name":"Biophysical journal","volume":" ","pages":"5718-5738"},"PeriodicalIF":3.7,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148886346","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":"Effects of an alkane on the adsorption and collapse by the lipids of pulmonary surfactant.","authors":"Ryan W Loney, Thomas M Weiss, Shankar B Rananavare, Stephen B Hall","doi":"10.1016/j.bpj.2026.08.002","DOIUrl":"10.1016/j.bpj.2026.08.002","url":null,"abstract":"<p><p>Pulmonary surfactant adsorbs rapidly to the surface of the liquid layer that lines the alveolar air sacs of the lungs. When compressed by the decreasing alveolar surface area during exhalation, the adsorbed films avoid collapse from the air/liquid interface and reduce surface tension to exceptionally low levels. Results with factors that induce surfactant lipids to increase intrinsic curvature suggest that adsorption proceeds via a curved rate-limiting structure. Samples with negative intrinsic curvature, defined by a concave hydrophilic surface, adsorb rapidly, but they also desorb quickly. Prior reports show that by optimizing chain packing, n-tetradecane (td) can promote conversion of planar bilayers to the negatively curved cylindrical monolayers of the inverse hexagonal phase without changing intrinsic curvature. The studies here show that td increases the rate of adsorption by the complete set of surfactant lipids without affecting intrinsic curvature and without promoting desorption of the adsorbed film during compression.</p>","PeriodicalId":8922,"journal":{"name":"Biophysical journal","volume":" ","pages":"5516-5525"},"PeriodicalIF":3.7,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13604018/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148688475","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lamin A depletion and RSG influence PPARγ DNA binding and chromatin organization in murine adult fibroblast cells.","authors":"Pialy Sen, Anshu Kumar Sharma, Arpan Chowdhury, Éva Hegedüs, László Imre, Ibtissem Benhamza, Julianna Volkó, Péter Szücs, László Nagy, Gábor Szabó, Péter Nagy, Katalin Tóth, György Vámosi","doi":"10.1016/j.bpj.2026.05.028","DOIUrl":"10.1016/j.bpj.2026.05.028","url":null,"abstract":"<p><p>Lamin A/C proteins, integral to the nuclear lamina and present throughout the nucleoplasm, contribute to the mechanical stability of the nucleus and influence transcription as seen in laminopathies like certain lipodystrophies and progeria. By using light-sheet fluorescence correlation spectroscopy (FCS), earlier, we proved that lamin A is an important determinant of chromatin viscoelasticity in murine adult fibroblasts (MAFs). Here, by using MAF wild-type and lamin A knockout (KO) cells, we aimed to clarify the role of lamin A in chromatin organization and the DNA binding of PPARγ, a key transcription factor in adipogenesis also implicated in lipodystrophies. We analyzed the distribution of chromatin marks by confocal microscopy and measured PPARγ mobility and DNA binding by FCS and fluorescence recovery after photobleaching (FRAP). Conspicuous overall changes were detected upon lamin A depletion and PPARγ agonist (rosiglitazone) treatment. Confocal imaging showed a remarkable decrease in nuclear volume in the absence of lamin A and an increase upon rosiglitazone treatment indicating chromatin decondensation. Heterochromatin was enriched in a distinct peripheral rim, and the thickness of the constitutive heterochromatin rim diminished in the absence of lamin A. Colocalization analysis showed that the overlap between euchromatin and heterochromatin decreased in lamin A KO cells. PPARγ colocalized with euchromatin, whereas its localization was anti-correlated with constitutive heterochromatin, especially in the absence of lamin A. FCS and FRAP indicated that PPARγ had a fast-diffusing fraction bound with short residence times on DNA and a slow, more stably bound fraction throughout the nucleus including the periphery. Rosiglitazone increased PPARγ's colocalization with the euchromatin and enhanced its DNA binding, which was more pronounced in lamin A KO cells. Our results suggest that lamin A plays a primary role in determining nuclear volume and overall chromatin organization with likely functional consequences exemplified by regulating ligand-induced DNA binding of PPARγ, which may have epigenomic and transcriptional consequences.</p>","PeriodicalId":8922,"journal":{"name":"Biophysical journal","volume":" ","pages":"5449-5465"},"PeriodicalIF":3.7,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147986483","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":"An energy-based mathematical model of actin-driven protrusions in eukaryotic chemotaxis.","authors":"Samuel W S Johnson, Maddy Parsons, Ruth E Baker, Philip K Maini","doi":"10.1016/j.bpj.2026.08.001","DOIUrl":"10.1016/j.bpj.2026.08.001","url":null,"abstract":"<p><p>In eukaryotic cell chemotaxis, many cells extend and retract transient actin-driven protrusions at their membrane that facilitate both the detection of external chemical gradients and directional movement via cell-matrix coupling and traction. Although extensive experimental work has detailed how cellular protrusions and morphology vary under different environmental conditions, the mechanistic principles linking protrusive activity to these factors remain poorly understood. Here, we model the extension of actin-based protrusions in chemotaxis as an optimization problem, wherein cells balance the detection of chemical gradients with the energetic cost of protrusion formation. Our model, built on the assumption of maximal energetic efficiency during migration, provides a framework that qualitatively reproduces experimentally observed patterns of protrusive activity across a range of biological systems and environmental conditions, suggesting that energetic efficiency may underpin the morphology and chemotactic behavior of motile eukaryotic cells. Additionally, we leverage the model to generate novel predictions regarding cellular responses to other, experimentally untested environmental perturbations, providing testable hypotheses for future experimental work that may be used to validate and refine the model presented here.</p>","PeriodicalId":8922,"journal":{"name":"Biophysical journal","volume":" ","pages":"5494-5515"},"PeriodicalIF":3.7,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148688492","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":"A Mechanochemical Model for Frequency Entrainment and Bursting Transitions in Cardiac Calcium Oscillations","authors":"Weijian Wang, Jinjiang Xie, Jun Zhou, Yuehua Yang, Hongyuan Jiang","doi":"10.1016/j.bpj.2026.09.034","DOIUrl":"https://doi.org/10.1016/j.bpj.2026.09.034","url":null,"abstract":"Rhythmic contraction of cardiomyocytes is driven by self-sustained intracellular calcium oscillations. While these oscillations are typically attributed to intrinsic calcium cycling, increasing experimental evidence indicates that external mechanical forces can modulate calcium oscillation frequency and lead to frequency entrainment. However, the physical mechanisms underlying such mechanical entrainment remain unclear. Here, we develop a minimal mechanochemical model that couples intracellular calcium cycling, adaptive ryanodine receptor (RyR) gating, and strain-induced reactive oxygen species (ROS) signaling to investigate how external mechanical forces reshape the nonlinear dynamics of autonomous calcium oscillations in cardiomyocytes. Linear stability analysis reveals that RyR inactivation is a slow adaptive variable that sets the intrinsic calcium oscillation timescale and stabilizes limit-cycle dynamics. Within this framework, external mechanical forces act as a parametric perturbation that reshapes the phase-space structure of the oscillator. We show that periodic forces induce frequency entrainment within a finite locking range, followed by a transition to a bursting-like regime as the force frequency exceeds a critical threshold. This transition boundary is further tunable by the balance between ROS production and clearance, which controls the effective sensitivity of the oscillator. These results thus establish a quantitative dynamical framework linking RyR channel kinetics to the stability and synchronization of cardiac calcium oscillations, and provide mechanistic insight into frequency-dependent mechanochemical coupling in cardiomyocytes.","PeriodicalId":8922,"journal":{"name":"Biophysical journal","volume":"41 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149087211","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":"Modeling Protein Diffusion Across ER–Nuclear Envelope Junctions Reveals Efficient Transport via Simple Diffusion","authors":"Carmela Moschella,Julia Scholz,Sara Merino-Aceituno,Christian Schmeiser,Shotaro Otsuka","doi":"10.1016/j.bpj.2026.10.002","DOIUrl":"https://doi.org/10.1016/j.bpj.2026.10.002","url":null,"abstract":"","PeriodicalId":8922,"journal":{"name":"Biophysical journal","volume":"9 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149090197","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":"Reflectin Proteins Form Net Charge Density-Tuned Multiphase Condensates That May Facilitate Spatial Organization in Squid Skin Bragg Lamellae","authors":"Reid Gordon,Robert Levenson,Brandon Malady,Yahya Al Sabeh,Daniel E. Morse","doi":"10.1016/j.bpj.2026.09.039","DOIUrl":"https://doi.org/10.1016/j.bpj.2026.09.039","url":null,"abstract":"","PeriodicalId":8922,"journal":{"name":"Biophysical journal","volume":"37 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149090196","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":"VARIANT: Web Server for Decoding and Analyzing Viral Mutations at Genome and Protein Levels","authors":"Rui Wang,Xuhang Dai,Xin Cao,Changchuan Yin,Tamar Schlick,Guo-Wei Wei","doi":"10.1016/j.bpj.2026.10.001","DOIUrl":"https://doi.org/10.1016/j.bpj.2026.10.001","url":null,"abstract":"","PeriodicalId":8922,"journal":{"name":"Biophysical journal","volume":"483 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149090195","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":"Mechanisms of protein transport between subcompartments of the cone photoreceptor outer segment membrane system","authors":"Alexey A. Tokarev, Peter D. Calvert","doi":"10.1016/j.bpj.2026.09.043","DOIUrl":"https://doi.org/10.1016/j.bpj.2026.09.043","url":null,"abstract":"(≤300 words, current = 296): Retinal cone photoreceptor outer segments (COS) are modified cilia where light is transduced into electrical signals. While extensive ultrastructural studies have established that the COS membrane system consists of several hundred parallel lamellae interconnected by the ciliary plasma membrane (PM) through narrow membrane bridges known as saddle points (SP), little is known about how components of the phototransduction cascade are delivered to COS, how they are loaded into flat lamellae surfaces (LS) and how they maintain uniform distribution among lamellae, especially in light of the steeply tapered lamellar geometry found in some species and high membrane turnover rate. Here, we quantify interlamellar membrane protein flux in Xenopus COS using a neutral membrane probe – the transmembrane domain of syntaxin 3 fused with EGFP (EGFP-Stx3TM), and develop 3D and 1D computational models of protein transport within the COS membrane system. The models describe diffusional transport of the probes along the folded membranes accounting for effects of molecular crowding. Axial equilibration of EGFP-Stx3TM in FRAP experiments is quantitatively described by the model based on diffusional transport, alone. The diffusion coefficient on the PM obtained from the model fitted to experimental data is approximately equal to that on the LS. Sensitivity analysis of the model shows that, surprisingly, SP contribute only ∼15% control of axial transport while the chief control, ∼80%, is located at the PM, and this control distribution is robust to changes in conditions. Thus, COS plasma membrane acts as a shunt conducting free transmembrane proteins between lamellae by Brownian diffusion, even in the presence of crowding effects and complex membrane geometry, while lamellae are capacitive sources/sinks. Axial Stx3TM flux can exceed 100 molecules/s suggesting that if opsins diffuse freely, their flux may exceed 104 molecules/s, supporting rapid equilibration and uniform distribution throughout the contiguous COS membrane system.","PeriodicalId":8922,"journal":{"name":"Biophysical journal","volume":"70 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149087212","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":"In Vitro Wrapping of Non-Enveloped Viral Capsids with Lipid Bilayers","authors":"Ana Luisa Duran-Meza, María Verónica Villagrana-Escareño, Rubén Darío Cadena-Nava, Jaime Ruiz-García, Charles M. Knobler, William M. Gelbart","doi":"10.1016/j.bpj.2026.09.029","DOIUrl":"https://doi.org/10.1016/j.bpj.2026.09.029","url":null,"abstract":"<ce:italic>In vitro</ce:italic> reconstituted virus-like particles (VLPs) – particles with structure identical to those of virus particles except for containing non-infectious genetic information instead of a viral genome – are promising nanocarriers for delivery of therapeutic cargos. Among the simplest examples are the VLPs formed from the capsid protein (CP) of either Cowpea Chlorotic Mottle Virus (CCMV) or Brome Mosaic Virus (BMV), which form spontaneously from purified components upon mixing CCMV or BMV CP with single-stranded RNA under the right pH and ionic strength conditions. The structure of these VLPs is identical to that of the virus particles, consisting of 180 copies of the CP organized as 12 icosahedrally-symmetric pentamers separated by 20 hexamers. In contrast, most viruses that infect mammalian cells are enveloped by a lipid bilayer filled with transmembrane virally-encoded glycoproteins, and it has not yet proved possible to reconstitute these particles from their purified components. To take advantage of the robustness of unenveloped virus capsids and the biocompatibility of lipid-bilayer-wrapped enveloped viruses, we demonstrate <ce:italic>in vitro</ce:italic> lipid-bilayer wrapping of intact plant viral (CCMV and BMV) capsids. Lipid compositions are chosen to match the opposite charge of the viral capsid, to promote stable membrane association. Our results provide an important first step toward the wrapping of <ce:italic>in vitro</ce:italic> reconstituted VLPs containing therapeutic mRNA. These enveloped virus-like particles (eVLPs) combine the stability and scalability of plant virus capsids with the functional advantages of lipid envelopes, advancing their potential as platforms for RNA delivery, vaccine design, and therapeutic nanotechnology.","PeriodicalId":8922,"journal":{"name":"Biophysical journal","volume":"1 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149087214","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}