Cellular and molecular bioengineering最新文献

{"title":"Characterization of diffusivity and mechanical properties of polyethylene glycol hydrogel conformal coatings over time for application in beta cell replacement therapy for type 1 diabetes.","authors":"Noa H deHaseth, Grisell C Gonzalez, Aaron A Stock, Ana L Claure, Gabriela Orlando, Alice A Tomei, Noel M Ziebarth","doi":"10.1007/s12195-025-00878-7","DOIUrl":"10.1007/s12195-025-00878-7","url":null,"abstract":"<p><strong>Purpose: </strong>Type 1 diabetes (T1D) is an autoimmune disorder that causes selected destruction of insulin-secreting pancreatic beta cells leading to insulin deficiency, hyperglycemia, and long-term complications. T1D has no cure and is primarily self-managed with blood sugar monitoring and exogenous insulin injections, which do not enable proper metabolic control and decreases patient's and caregivers' quality of life. Beta cell replacement through islet transplantation could cure T1D if current limitations such as the need for chronic systemic immunosuppression to prevent rejection and recurrence of autoimmunity are addressed. A potential new treatment addressing these limitations is based on transplantation of donor islets encapsulated in hydrogels with suitable and stable permselectivity and mechanical properties. Specifically, these hydrogel coatings must be (<i>1</i>) permeable to nutrients, insulin and glucose, necessary for coated cell viability and functionality, but impermeable to antibodies, to enable immune isolation, and (<i>2</i>) resistant to degradation, over time.</p><p><strong>Methods: </strong>This study uses Fluorescence Recovery after Photobleaching (FRAP) and Atomic Force Microscopy (AFM) to determine the diffusion coefficient and Young's modulus of elasticity of individual model beads and primary and pseudoislets conformally coated with polyethylene glycol (PEG) over an extended period of time to evaluate the stability and viability of this novel therapeutic method for beta cell replacement without immunosuppression in T1D.</p><p><strong>Results: </strong>The conformal hydrogel coatings remained functional and did not deteriorate over the 100-day time period, showing a promising stability to enable long-term immunoisolation of encapsulated islets.</p><p><strong>Conclusions: </strong>This report demonstrated a novel measurement technique capable of assessing the mechanical and transport properties of individually coated samples, giving a more precise characterization of inherent variabilities within a sample population. Moreover, the approach is adaptable to other therapeutic cell clusters and organoids, supporting broader applications in cell transplantation therapies and offering a robust method for batch release validation in clinical applications.</p>","PeriodicalId":9687,"journal":{"name":"Cellular and molecular bioengineering","volume":"18 6","pages":"611-623"},"PeriodicalIF":5.0,"publicationDate":"2025-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12664873/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145653635","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An Update on AI Hallucinations: Not as Bad as You Remember or as You've Been Told.","authors":"Michael R King","doi":"10.1007/s12195-025-00874-x","DOIUrl":"https://doi.org/10.1007/s12195-025-00874-x","url":null,"abstract":"","PeriodicalId":9687,"journal":{"name":"Cellular and molecular bioengineering","volume":"18 6","pages":"543-548"},"PeriodicalIF":5.0,"publicationDate":"2025-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12664859/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145653579","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Quantitative Analysis of Monocyte-Derived Macrophage NFκB Signaling in Cancer Co-culture Models Using Luciferase-Based Biosensing.","authors":"Colette Li, Megha Anand, Garrett McPheron, Maeve Stiles, Elizabeth Wayne","doi":"10.1007/s12195-025-00870-1","DOIUrl":"10.1007/s12195-025-00870-1","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background and purpose: &lt;/strong&gt;In this study, we investigate the plasticity of tumor-associated macrophages, which originate from circulating monocytes and are associated with poor cancer prognosis. The differentiation of monocytes into macrophages is a dynamic and spatiotemporal process, as is the resulting macrophages' polarization. However, traditional methods for measuring polarization, such as qPCR and flow cytometry, provide only static information about polarization. To supplement these methods, we present a novel bioluminescent method that allows for time-resolved measurement of NFκB activation in macrophages while in co-culture with cancer cells. By using a monocyte cell line whose NFκB responsive element is labeled with firefly luciferase, we obtain a quantitative and temporal characterization of macrophage polarization in response to tumor-derived signals.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Materials and methods: &lt;/strong&gt;To quantify the effect of tumor cell signaling THP-1 monocytes encoded with a firefly luciferase NFκB response element were co-cultured with cancer cells. We investigated the impact of the following factors on NFκB signaling cancer cell type (HCT116 or MDA-MB-231), ratio of the number of cancer cells to macrophages in co-culture, and the THP-1 cell differentiation state (monocyte or monocyte-derived macrophage). Bioluminescence was measured over three days. Descriptive features of the bioluminescence response curves were then extracted to compare effects between cancer types.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;We observed that the MDA-MB-231 cancer cells induced lower but more persistent NFκB activation in THP-1 monocyte-derived macrophages than was observed in HCT116 co-culture. Higher number of cancer cells (lower macrophage ratio) elicited higher AUC values in HCT116 co-culture compared to low cancer cell conditions. There was no difference between high and low macrophage ratios within the MDA-MB-231 co-culture condition. Moreover, the addition of macrophage differentiation stimuli modulated the NFκB profile in the co-culture. PMA-differentiated macrophages expressed higher and faster peaks of NFκB activation.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;Cancer cells can modulate monocyte/macrophage NFκB transcriptional activity, impacting the overall tumor microenvironment. Using NFκB reporter cells, we found that HCT116 colorectal cancer cells induced fast and strong NFκB activation profiles. In contrast, MDA-MB-231 cancer cells elicited lower but more persistent NFκB activation profiles. This study highlights how bioluminescence reporter assays can be used to extract meaningful metrics about monocyte/macrophage behavior during tumor progression. This approach could also be used to understand the crosstalk between cancer cells and monocytes/macrophages that could be useful in a therapeutic of diagnostic context.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Graphical abstract: &lt;/strong&gt;&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Supplementary information: &lt;/strong&gt;The online version contains s","PeriodicalId":9687,"journal":{"name":"Cellular and molecular bioengineering","volume":"18 5","pages":"419-432"},"PeriodicalIF":5.0,"publicationDate":"2025-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12579604/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145437142","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The 2025 Young Innovators of Cellular and Molecular Bioengineering.","authors":"Edward A Sander, Sarah Calve, Lauren D Black","doi":"10.1007/s12195-025-00876-9","DOIUrl":"https://doi.org/10.1007/s12195-025-00876-9","url":null,"abstract":"","PeriodicalId":9687,"journal":{"name":"Cellular and molecular bioengineering","volume":"18 5","pages":"323-325"},"PeriodicalIF":5.0,"publicationDate":"2025-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12579640/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145437198","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cyclic Hydrostatic Pressure Suppresses Osteogenic Differentiation via Actomyosin Contractility.","authors":"Takashi Miyano, Toshihiro Sera","doi":"10.1007/s12195-025-00875-w","DOIUrl":"https://doi.org/10.1007/s12195-025-00875-w","url":null,"abstract":"<p><strong>Purpose: </strong>The periodontal ligament (PDL), which contains osteoblasts, is a unique connective tissue that resists mineralization despite being located between mineralized cementum and alveolar bone. The role of physiological mechanical stress, particularly the cyclic hydrostatic pressure (HP) generated during mastication, in regulating osteogenic potential remains poorly understood. This study aimed to compare the effects of static and cyclic HP on osteogenic differentiation and to elucidate the underlying mechanisms.</p><p><strong>Methods: </strong>A custom-built pressure-loading device was developed to apply either static or cyclic HP to MC3T3-E1 pre-osteoblastic cells. These cells, which are widely used as models for osteogenic differentiation, were subjected to conditions mimicking PDL-relevant mechanical environments. Osteogenic differentiation was evaluated using alkaline phosphatase (ALP) activity assays. Actomyosin contractility was assessed through immunofluorescence staining of focal adhesions using vinculin, along with phosphorylated myosin light chain (p-MLC) to assess myosin activity. To examine the role of actomyosin contractility, cells were treated with blebbistatin, a myosin II inhibitor.</p><p><strong>Results: </strong>Compared to static HP (5 MPa), cyclic HP (5 MPa, 0.2 Hz) more strongly inhibited ALP activity. HP stimulation enhanced both focal adhesion formation and p-MLC levels, with the latter showing a markedly greater increase under cyclic HP than static HP. Notably, inhibition of p-MLC phosphorylation with 10 μM blebbistatin attenuated these HP-induced effects, indicating that actomyosin contractility plays a critical role in mediating the suppression of osteogenic differentiation.</p><p><strong>Conclusions: </strong>Cyclic HP more effectively inhibited osteogenic differentiation than static HP, likely through enhanced actomyosin contractility associated with increased p-MLC expression in MC3T3-E1 pre-osteoblastic cells.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s12195-025-00875-w.</p>","PeriodicalId":9687,"journal":{"name":"Cellular and molecular bioengineering","volume":"18 6","pages":"625-636"},"PeriodicalIF":5.0,"publicationDate":"2025-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12664866/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145653622","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lysophosphatidic Acid (LPA) Receptor Signaling Promotes the Adaptation of Malignant Cellular Functions in Highly Migratory Osteosarcoma Cells Under Hypoxic and Low-Glucose Conditions.","authors":"Anri Taniguchi, Moemi Tamura, Mao Yamamoto, Narumi Yashiro, Yuka Kusumoto, Shion Nagano, Nanami Shimomura, Miwa Takai, Toshifumi Tsujiuchi","doi":"10.1007/s12195-025-00873-y","DOIUrl":"https://doi.org/10.1007/s12195-025-00873-y","url":null,"abstract":"<p><strong>Purpose: </strong>In solid tumors, cancer cells adapt to hypoxic and nutrient deprived environments to support malignant progression. This study examined whether hypoxic and low glucose conditions enhance malignant behaviors more strongly in highly migratory MG63-R10 cells, which are derived from osteosarcoma MG-63 cells, compared to parental MG-63 cells, and further investigated whether lysophosphatidic acid (LPA) receptor signaling regulates this adaptation.</p><p><strong>Methods: </strong>MG63-R10 and MG-63 cells were cultured under hypoxic (1% O₂) or normoxic (21% O₂) conditions in media containing 4500, 2000, or 1000 mg/L glucose. LPA receptor expression was analyzed by quantitative real time RT-PCR. Cell growth and motility were assessed, and pharmacological modulators AM966 (LPA₁ antagonist), GRI-977143 (LPA₂ agonist), and (2S)-OMPT (LPA₃ agonist) were used to evaluate receptor specific effects on cell growth and motility.</p><p><strong>Results: </strong>Under 1% O₂, <i>LPAR2</i> expression increased in MG63-R10 cells, while <i>LPAR1</i> and <i>LPAR3</i> expression decreased. MG63-R10 cells showed lower growth than MG-63 cells under 21% O₂, but higher growth under hypoxia. MG63-R10 cell motility was higher than that of MG-63 cells at 21% O₂ and was further enhanced under 1% O₂. AM966 and GRI-977143 increased MG63-R10 motility, whereas (2S)-OMPT suppressed it. MG63-R10 motility significantly increased in 2000 and 1000 mg/L glucose, whereas MG-63 motility remained unchanged across glucose levels.</p><p><strong>Conclusion: </strong>These results suggest that, compared to parental MG-63 cells, highly migratory osteosarcoma MG63-R10 cells adapt their malignant cellular functions to hypoxic and low-glucose conditions through LPA receptor signaling, highlighting this pathway as a potential therapeutic target in aggressive osteosarcomas.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s12195-025-00873-y.</p>","PeriodicalId":9687,"journal":{"name":"Cellular and molecular bioengineering","volume":"18 6","pages":"577-588"},"PeriodicalIF":5.0,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12664869/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145653713","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"G Protein-Coupled Estrogen Receptor Regulates Mesenchymal Stem Cell Mechanotransduction and Differentiation.","authors":"Hao Wang, Ofra Ben Menachem-Zidon, Ashish Pandey, Yue Xiao, Nanzhong Deng, Xiaojie Shi, Amparo Ruiz, Yi Ye, Haogang Cai","doi":"10.1007/s12195-025-00867-w","DOIUrl":"10.1007/s12195-025-00867-w","url":null,"abstract":"<p><strong>Introduction: </strong>G protein-coupled estrogen receptor (GPER) is a heptahelix estrogen-binding G protein-coupled receptor, and a potential therapeutic target for estrogen-related cancers and diseases. Recently, GPER has been recognized as a key mechano-regulator, but the effects on cell adhesion, spreading, morphology, migration, and differentiation are inconsistent or even contradicting in literature, due to the variations across cell lines and complex crosstalks with ER, and non-genomic actions of other hormones. Here, we focus on investigating the GPER effect on mesenchymal stem cell (MSC) mechanotransduction and differentiation.</p><p><strong>Methods: </strong>MSCs treated by synthetic agonist G1 and untreated cells were cultured on fibronectin-coated surfaces. Cell migration was studied by both chemokinesis and chemotaxis experiments. After two-week differentiation, MSC adipogenesis and osteogenesis were evaluated by staining lipid droplets in adipocytes with Oil-Red O and alkaline phosphatase in osteocytes with NBT/BCIP, respectively. In particular, since micropatterns have been widely used to mimic extracellular matrix (ECM) cues, modulate MSC mechanotransduction and differentiation, we investigate the GPER effect on both single-cell and sub-cellular fibronectin microline patterns prepared by microcontact printing.</p><p><strong>Results: </strong>GPER activation regulates cytoskeleton organization, with reduced cell polarization, thinner ventral stress fibers, and reduced RhoA signaling; reduces MSC migration speed; significantly promotes osteogenesis and inhibits adipogenesis. Cell elongation by micropatterns and the reduction of cell polarization by GPER coexist in a sophisticated interplay.</p><p><strong>Conclusions: </strong>GPER directly mediates MSC mechanotransduction by RhoA inactivation, while its sustained effect on MSC differentiation promotes osteogenesis and inhibits adipogenesis despite reduced cell polarization and tension, suggesting potential mechanisms other than RhoA signaling. Our findings pave the way towards a deep understanding of GPER's role and its interplay with ECM cues in mechanotransduction and differentiation, which will be important for developing GPER as a new therapeutic target, as well as considering its important effects in stem cell therapies and hormonal therapies.</p>","PeriodicalId":9687,"journal":{"name":"Cellular and molecular bioengineering","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12530058/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145328338","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metabolomic Profiling and Characterization of a Novel 3D Culture System for Studying Chondrocyte Mechanotransduction.","authors":"Priyanka P Brahmachary, Ayten E Erdogan, Erik P Myers, Ronald K June","doi":"10.1007/s12195-025-00872-z","DOIUrl":"10.1007/s12195-025-00872-z","url":null,"abstract":"<p><strong>Purpose: </strong>Articular chondrocytes synthesize and maintain the avascular and aneural articular cartilage. In vivo these cells are surrounded by a 3D pericellular matrix (PCM) containing predominantly collagen VI. The PCM protects chondrocytes and facilitates mechanotransduction. PCM stiffness is critical in transmitting biomechanical signals to chondrocytes. Various culture systems with different hydrogels are used to encapsulate chondrocytes for 3D culture, but many lack either the PCM or the in vivo stiffness of the cartilage matrix. This study aimed at establishing a culture system to investigate (a) if chondrocytes cultured in alginate will develop a PCM and (b) study mechanotransduction via metabolic changes induced in 3D agarose-embedded chondrocytes upon mechanical stimulation.</p><p><strong>Methods: </strong>We cultured primary human and bovine chondrocytes in monolayers or as alginate encapsulated cells in media containing sodium L-ascorbate. PCM expression was analyzed by immunofluorescence and western blots. We further characterized the response of chondrocytes embedded in physiologically stiff agarose to dynamic compression through metabolomic profiling.</p><p><strong>Results: </strong>We found that primary human and bovine chondrocytes, when cultured in alginate beads with addition of sodium L-ascorbate for 7 days, had a pronounced PCM, retained their phenotype, and synthesized both collagens VI and II. This novel culture system enables alginate-encapsulated chondrocytes to develop a robust PCM thereby creating a model system to study mechanotransduction in the presence of an endogenous PCM. We also observed distinct compression-induced changes in metabolomic profiles between the monolayer-agarose and alginate-released agarose-embedded chondrocytes indicating physiological changes in cell metabolism.</p><p><strong>Conclusion: </strong>These data show that 3D preculture of chondrocytes in alginate before encapsulation in physiologically stiff agarose leads to pronounced development of pericellular matrix that is sustained in the presence of ascorbate. This model can be useful in studying the mechanism by which chondrocytes respond to cyclical compression and other types of loading simulating in vivo physiological conditions.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s12195-025-00872-z.</p>","PeriodicalId":9687,"journal":{"name":"Cellular and molecular bioengineering","volume":"18 6","pages":"589-609"},"PeriodicalIF":5.0,"publicationDate":"2025-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12664864/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145653769","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Paracrine Signaling by Distinct Adipose Tissue Depots Regulate Fibroblast Mechanobiology and Functional Heterogeneity.","authors":"Yujun Xu, Niyousha Karbasion, Tata A Toure, Jack A Esche, Brendan K Otani, J Caleb Snider, Matthew R Bersi","doi":"10.1007/s12195-025-00864-z","DOIUrl":"https://doi.org/10.1007/s12195-025-00864-z","url":null,"abstract":"<p><strong>Purpose: </strong>Adipose tissues have long been recognized for their diverse endocrine functions that serve to regulate tissue homeostasis. Although adipose depot-specific secretory profiles can differentially regulate fibroblast fate and fibrotic tissue remodeling, systematic investigation of how adipose depots of varying phenotypes influence fibroblast mechanobiology remains lacking.</p><p><strong>Methods: </strong>By integrating secretome profiling with functional and mechanobiological assays in a controlled adipose-fibroblast coculture platform, we mechanistically investigate how canonical brown (BAT), white (WAT), and beige adipose tissues (thoracic and abdominal perivascular adipose tissue; T-PVAT and A-PVAT, respectively) govern fibroblast-to-myofibroblast transition (FMT) through depot-specific paracrine signaling.</p><p><strong>Results: </strong>Thermogenic depots (BAT and T-PVAT) enhance fibroblast proliferation, collagen deposition, and stiffness (1.9-fold increase in single cell modulus; <i>p</i> < 0.0001) alongside specific adipokines that regulate metabolism (ANGPTL3, FGF1) and inhibit calcification (Fetuin A). In contrast, lipid-storing depots (WAT and A-PVAT) promote fibroblast migration (79% scratch wound closure at 12 h; <i>p</i> < 0.01) and matrix degradation through upregulated pro-inflammatory cytokines (CCL2, IL-6) and fibrogenic mediators (PAI-1, TIMP-1). Mechanistically, BAT and T-PVAT secretomes induce pro-contractile and matrix-producing fibroblast phenotypes, while A-PVAT and WAT promote migratory and matrix-remodeling behaviors. Further, T-PVAT uniquely combines BAT-like genetic identity with elevated RAGE-DPP4 signaling, resulting in excessive fibroblast activation, stiffening, and collagen production that can be attenuated via pharmacological inhibition of DPP4.</p><p><strong>Conclusions: </strong>Our findings establish adipose depots as distinct modulators of fibroblast phenotype, wherein depot-specific mediators promote mechanobiological alterations that balance reparative and pathological remodeling processes related to fibrosis. Differential biological responses by fibroblasts exposed to diverse adipose phenotypes underscores the potential for adipose-driven stromal crosstalk to mitigate fibrotic remodeling alongside metabolic and cardiovascular disease comorbidities.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s12195-025-00864-z.</p>","PeriodicalId":9687,"journal":{"name":"Cellular and molecular bioengineering","volume":"18 5","pages":"327-346"},"PeriodicalIF":5.0,"publicationDate":"2025-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12579652/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145437080","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Formins and Arp2/3 Reciprocally Regulate Contact Guidance on Aligned Collagen Fibrils.","authors":"Azarnoosh Foroozandehfar, Shayan Tohidi, Shafayet Ahmed Siddiqui, Fred Rogers Namanda, Michael Forrester, Eric Cochran, Ian C Schneider","doi":"10.1007/s12195-025-00868-9","DOIUrl":"10.1007/s12195-025-00868-9","url":null,"abstract":"<p><strong>Motivation: </strong>Directed cell migration is essential in many biological processes and is driven by a variety of directional cues, including aligned fibrils in the extracellular matrix (ECM), a phenomenon known as contact guidance. How different cells respond to aligned fibrils and how internal regulators like formins and Arp2/3 control contact guidance is unknown.</p><p><strong>Methods: </strong>In this study, a unique system to assemble aligned collagen fibrils on mica and to transfer them onto controllable substrates is used to probe contact guidance.</p><p><strong>Results: </strong>This fibril alignment system reveals that cytoskeletal regulation through myosin contractility and not receptor expression drives contact guidance ability. Highly contractile cells exhibit high-fidelity contact guidance, weakly contractile cells ignore cues and moderately contractile cells use a mixture of both parallel and perpendicular migration strategies on aligned collagen fibrils. In addition to myosin contractility, formins and Arp2/3 control contact guidance in a reciprocal manner across a variety of cell types. Formins, mediators of linear F-actin structures, enhance contact guidance and Arp2/3, a mediator of branched F-actin structures, diminishes contact guidance.</p><p><strong>Conclusion: </strong>This controlled materials system reveals the importance of both myosin-mediated contractility as well as the antagonistic action of formins and Arp2/3 on contact guidance, providing potential targets to tune contact guidance.</p><p><strong>Graphical abstract: </strong></p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s12195-025-00868-9.</p>","PeriodicalId":9687,"journal":{"name":"Cellular and molecular bioengineering","volume":"18 6","pages":"637-659"},"PeriodicalIF":5.0,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12664870/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145653691","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}