Biology of the Cell最新文献

{"title":"The Chronological Trigger: The Orchestra Between Homeobox Genes and the Circadian Clock During Development","authors":"Joice de Faria Poloni,&nbsp;Bruno César Feltes","doi":"10.1111/boc.70027","DOIUrl":"https://doi.org/10.1111/boc.70027","url":null,"abstract":"<p>As master regulators of embryonic development, regulating homeobox genes is fundamental for developmental biology. Despite the growth of multiple topics regarding fine-tuning homeobox gene expression, the discussion on how the circadian rhythm affects their control and vice-versa still needs to be improved. Due to the intrinsic importance of the circadian clock and its impact on several molecular mechanisms, including development and pregnancy, the interplay between this mechanism and homeobox genes becomes a meaningful discussion. This work aims to review and critically discuss the crosstalk between homeobox genes and circadian regulation in multiple organisms, focusing on differentiation and developmental mechanisms. A considerable focus is given to new perspectives on the topic.</p>","PeriodicalId":8859,"journal":{"name":"Biology of the Cell","volume":"117 7","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/boc.70027","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144695794","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Meeting Report on the Symposium Organized to Celebrate the 40th Anniversary of the French Society for Cell Biology","authors":"Florence Niedergang,&nbsp;Renaud Chabrier,&nbsp;Isabelle Tardieux","doi":"10.1111/boc.70014","DOIUrl":"https://doi.org/10.1111/boc.70014","url":null,"abstract":"<p>The French Society for Cell Biology (SBCF) gathers all researchers working in the broad field of cell biology and is actively involved in several missions. Indeed, from communicating about the latest breakthroughs to announcing upcoming events, the SBCF also identifies and nurtures emerging talents while financially supporting young researchers to help them attend scientific meetings. The society's mission is to promote the scientific area, to boost knowledge transmission, and be the reference for French research in cell biology on the international stage. In this context, the SBCF has woven networks of knowledge and expertise with global Societies of cell biology and continues to foster partnerships specifically through joint sessions at international meetings. In the same vein, since 2022, the SBCF has been organizing an annual themed international symposium called “Cell Biology of…” to spotlight specific topics of interest. Past editions have highlighted subjects such as the coronaviruses, neurons, and plants, showcasing the broad scope of the discipline. In addition to these scientific initiatives, the SBCF is also very much committed to supporting and regularly organizing a variety of events for raising the public awareness of science in general and cell biology in particular, and engaging it in the wonders of science.</p>","PeriodicalId":8859,"journal":{"name":"Biology of the Cell","volume":"117 7","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/boc.70014","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144635339","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dynamic Organization of Cells in Colonic Epithelium is Encoded by Five Biological Rules","authors":"Bruce M. Boman,&nbsp;Thien-Nam Dinh,&nbsp;Keith Decker,&nbsp;Brooks Emerick,&nbsp;Shirin R. Modarai,&nbsp;Lynn M. Opdenaker,&nbsp;Jeremy Z. Fields,&nbsp;Christopher Raymond,&nbsp;Gilberto Schleiniger","doi":"10.1111/boc.70017","DOIUrl":"https://doi.org/10.1111/boc.70017","url":null,"abstract":"<p>Tissue organization is fundamental to the form and function of most, if not all, multicellular organisms. But what specifies the precise histologic organization of cells in tissues of plants and animals is unclear. We hypothesize that a <i>tissue code</i> exists that is the basis for dynamic maintenance of tissue organization. Any code for tissue organization must account for how the dynamics of tissue renewal maintain histologic structure. Accordingly, we modeled the dynamics of crypt renewal to determine how the organization of cells is maintained in colonic epithelium. Specifically, we modeled spatial and temporal asymmetries of cell division and established that five simple mathematical laws ([1] timing of cell division, [2] temporal order of cell division, [3] spatial direction of cell division, [4] number of cell divisions, and [5] cell lifespan) constitute a set of biological rules for colonic epithelia. Our results indicate that these rules form the basis of precise organization of cells in colonic epithelium during continuous crypt renewal. These five laws might even provide a means to understand the mechanisms that underlie organization of other tissue types, and how genetic alterations cause tissue disorganization that leads to birth defects and tissue pathology like cancer.</p>","PeriodicalId":8859,"journal":{"name":"Biology of the Cell","volume":"117 7","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/boc.70017","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144615376","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Nuclear Envelope Proteins Esc1 and Mps3 Differentially Impact Sterol Gradients in Budding Yeast","authors":"Maria Laura Sosa Ponce,&nbsp;Roxana Valdés Núñez,&nbsp;Andrew Henderson,&nbsp;Suriakarthiga Ganesan,&nbsp;Colton M. Unger,&nbsp;Jennifer A. Cobb,&nbsp;Vanina Zaremberg","doi":"10.1111/boc.70024","DOIUrl":"https://doi.org/10.1111/boc.70024","url":null,"abstract":"<div>\u0000 \u0000 <p>The metabolically stable lysolipid analogue edelfosine is an antitumor/antiparasitic drug proposed to act by disrupting lipid rafts and reducing the accessible sterol pool at the plasma membrane (PM). Once internalized, edelfosine also induces deformation of the nuclear envelope (NE) and disrupts telomere clustering in yeast. In this study we investigate the impact that NE-chromatin-anchoring pathways have on PM and NE/ER sterol homeostasis. Cells lacking Sir4 (<i>sir4</i>Δ) of the Silent Information Regulator histone deacetylase complex are resistant to edelfosine despite NE deformation induced by the drug. Using live fluorescence microscopy, we show herein that in <i>sir4</i>Δ yeast sterols remain accessible at the PM and redistribute from the PM of daughter cells to the PM of mother cells in response to edelfosine. Since Sir4 is the scaffold component of the SIR complex that mediates telomere anchoring to the NE, we questioned if its interactors at the NE, Esc1, and Mps3, could also impact sterol mobilization in response to edelfosine. Cells lacking Esc1 mimicked the phenotypes of <i>sir4</i>Δ yeast in response to edelfosine. Unlike <i>sir4</i>Δ and <i>esc1</i>Δ yeast, cells carrying a truncated Mps3 unable to bind Sir4, <i>mps3</i>Δ65-145, displayed aberrant NE morphology, intracellular sterol punctate and sensitivity to edelfosine. Furthermore, significative differences in squalene to sterol esters ratios between <i>esc1</i>Δ and <i>mps3</i>Δ65-145 mutants were found. Altogether these results support a differential contribution of Esc1 and Mps3 to sterol homeostasis and establishment of its intracellular gradient. The Sir4-Esc1 interaction sensitizes cells to lysolipid toxicity and sterol transport from the PM, while Mps3 has a stronger influence on silencing and sterol retention capacity at the PM.</p>\u0000 </div>","PeriodicalId":8859,"journal":{"name":"Biology of the Cell","volume":"117 7","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144573224","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":"NSUN6 Maintains BMPER Stability in an m5C-Dependent Manner to Suppress Cell Proliferation and Migration in Hepatocellular Carcinoma","authors":"Chunlin Liu,&nbsp;Yumin Wu,&nbsp;Ying Wu,&nbsp;Weizhi Luo,&nbsp;Yuefei Hong,&nbsp;Leichang Jiang,&nbsp;Senrui Wang,&nbsp;Duanming Du","doi":"10.1111/boc.70023","DOIUrl":"https://doi.org/10.1111/boc.70023","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The expression of Nop2/Sun domain family member 6 (NSUN6), an RNA m5C methyltransferase, is correlated with the prognosis of various cancers. However, its role in the progression of hepatocellular carcinoma (HCC) remains elusive.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The expression of NSUN6 was analyzed using the TCGA-HCC cohort, as well as through quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) and western blotting in tumor tissues from HCC patients and various HCC cell lines. Moreover, its biological functions were detected using cell counting kit 8 (CCK8), colony formation, 5-ethynyl-2′-deoxyuridine (EdU), wound healing, and transwell invasion assays in vitro, as well as in an HCC patient-derived xenograft (PDX) mouse model in vivo. The molecular mechanism underlying NSUN6 was explored using methylated RNA immunoprecipitation sequencing (MeRIP-seq), double luciferase reporter gene assay, actinomycin-D assay, and rescue experiments in SNU449 cell lines.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The expression level of NSUN6 was significantly decreased in the TCGA-HCC cohort, tumor tissues of HCC patients and HCC cell lines. NSUN6 overexpression markedly inhibited the proliferative and migratory abilities of HCC cells in the PDX mouse model. Additionally, BMPER was identified as a downstream target of NSUN6, while NSUN6 could stabilize BMPER expression in an m5C-dependent manner. Finally, BMPER knockdown reversed the positive effects of NSUN6 in suppressing HCC progression.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This study elucidated the inhibitory effect of NSUN6 overexpression in HCC development, with BMPER identified as a downstream target of NSUN6. NSUN6 regulates BMPER expression in an m5C-dependent manner, thereby influencing HCC progression. Overall, these results suggest that the NSUN6/BMPER axis may serve as a potential therapeutic target for HCC.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8859,"journal":{"name":"Biology of the Cell","volume":"117 7","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/boc.70023","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144520268","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The DNA Repair Component EEPD1 Regulates Actin Polymerization","authors":"Robert Hromas,&nbsp;Austin Kirby,&nbsp;Andrew Carrillo,&nbsp;Aruna Jasiwal,&nbsp;Kimi Kong,&nbsp;Manh Tien Tran,&nbsp;Dominic Arris,&nbsp;Elizabeth A. Williamson","doi":"10.1111/boc.70022","DOIUrl":"https://doi.org/10.1111/boc.70022","url":null,"abstract":"<p>Endonuclease exonuclease phosphatase domain-containing protein 1 (EEPD1) is a DNase1 superfamily member that has DNA endonuclease activity. It plays a critical role in multiple DNA repair processes such as oxidative damage repair and stressed replication fork repair. Interestingly, EEPD1 is myristoylated and palmitoylated near its amino terminus in response to high levels of cholesterol, and this localizes EEPD1 protein to the inner cell membrane. Surprisingly, we found that EEPD1 promotes cortical branching actin polymerization and proper lamellipodia formation and is necessary for subsequent cell migration. EEPD1's enhancement of actin polymerization partially required its myristoylation and palmitoylation. EEPD1 depletion also resulted in marked abnormalities in nuclear morphology. Loss of EEPD1 resulted in loss of phosphorylation of SRC, RAC1, cortactin, and profilin, which are essential steps in signaling for actin polymerization. Loss of EEPD1 lowered SRC kinase activity, which would harm actin polymerization. In summary, EEPD1 is a novel, positive regulator of the signaling pathway for actin polymerization, linking actin regulation to nuclear morphology and DNA repair.</p>","PeriodicalId":8859,"journal":{"name":"Biology of the Cell","volume":"117 7","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/boc.70022","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144520307","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In Toto Adipocytes Analysis Using Hydrophilic Tissue Clearing, Light Sheet Microscopy, and Deep Learning-Based Image Processing","authors":"Dylan Le Jan,&nbsp;Manar Harb,&nbsp;Mohamed Siliman Misha,&nbsp;Jean-Claude Desfontis,&nbsp;Yassine Mallem,&nbsp;Laurence Dubreil","doi":"10.1111/boc.70013","DOIUrl":"https://doi.org/10.1111/boc.70013","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background Information</h3>\u0000 \u0000 <p>Obesity is a multifactorial metabolic disease characterized by excessive fat storage in adipocytes, particularly in visceral adipose tissue (VAT) like mesenteric adipocytes. Metabolic dysfunctions due to obesity are often associated with modification of adipocyte volume. Various techniques for measuring adipocyte size are described in the literature, including classical histological methods on paraffin-embedded tissue sections or dissociation of adipose tissue (AT) using collagenase with artifacts due to AT post treatment.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>This study aims to develop and implement an innovative method for 3D investigation of AT to assess adipocyte volume, overcoming the limitations and biases inherent in traditional techniques. The principle of the method relies on fluorescent labeling of lipids and extracellular matrix (ECM) in toto within AT, followed by a tissue clearing step without delipidation and imaging using 3D light sheet microscopy coupled with automated analysis of adipocyte size through a deep learning approach. By this work we showed that the volume of adipocytes increased in mesenteric AT from obese rats with an increase in the distance between adipocytes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion and Significance</h3>\u0000 \u0000 <p>The current work highlights the interest in combining AT clearing without a delipidation step and light sheet microscopy for in toto 3D adipocyte characterization in obese versus healthy rats. While this method is particularly valuable for understanding adipocyte hypertrophy in the context of obesity, its applicability extends beyond this area. This innovative approach offers valuable opportunities for investigating adipocyte dynamics in various pathological conditions, evaluating the impact of nutritional interventions, and assessing the effectiveness of pharmacological treatments.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8859,"journal":{"name":"Biology of the Cell","volume":"117 6","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/boc.70013","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144339242","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigating the Role of Proteins and Lipids in the Prevention of Nanoparticle-Induced Cellular Membrane Damage Using Engineered Biomimetic Vesicles","authors":"Mahsa Kheradmandi,&nbsp;Amir M. Farnoud,&nbsp;Monica M. Burdick","doi":"10.1111/boc.70020","DOIUrl":"https://doi.org/10.1111/boc.70020","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Although nanoparticles are promising tools for novel therapeutics, there is a need to better understand different mechanisms of cellular nanotoxicity. Several studies have investigated the intracellular cytotoxicity of nanoparticles after entering cells via endocytosis, but the impact on the plasma membrane remains unclear. Giant plasma membrane vesicles (GPMVs) serve as powerful models to study nanoparticle–membrane interactions while preserving the native lipid and protein composition, and eliminating endocytosis interference. This study focuses on understanding the mechanism underlying the disruptive effects of nanoparticles on the cell membrane using biomimetic GPMVs.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A549 cells were chemically induced to generate GPMVs. GPMV-like, protein-free vesicles were also synthesized to understand the role of membrane proteins in nanotoxicity. Lipid exchange was then employed to investigate the function of lipids in membrane integrity. These vesicles were utilized to study the mechanisms of nanoparticle–membrane cytotoxicity. Additionally, this study introduced a novel repairing method that utilizes surface engineering and chemical alterations to reconstruct the pores formed during vesiculation, offering a new method to enhance the stability of biomembranes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>This study is the first to demonstrate that membrane proteins significantly enhance the ability of biomembranes to interact and adsorb silica nanoparticles. Additionally, nanoparticle exposure induced more morphological damages in the protein-free compared to the protein-containing GPMVs. Furthermore, the exchange with glycerophospholipids containing one saturated acyl chain significantly improved the stability and fluidity of vesicles before and after exposure to different toxic nanoparticles. This work successfully introduces a new repairing technique for the loaded vesicles derived directly from the living cells to enhance the encapsulation efficiency and minimize the nanotoxicity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>In summary, membrane lipid saturation and selective protein incorporation are critical factors in nanoparticle binding, vesicle stability, and exogenously induced disruption of membrane-derived vesicles. These findings provide new insights into minimizing nanotoxicity while optimizing nanoparticle-based therapeutic applications.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8859,"journal":{"name":"Biology of the Cell","volume":"117 6","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144339243","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":"Protrusion-Derived Extracellular Vesicles (PD-EVs) and Their Diverse Origins: Key Players in Cellular Communication, Cancer Progression, and T Cell Modulation","authors":"Mireia Gomez Duro,&nbsp;Lucas Alves Tavares,&nbsp;Izadora Peter Furtado,&nbsp;Julien Saint-Pol,&nbsp;Gisela D'Angelo","doi":"10.1111/boc.70018","DOIUrl":"https://doi.org/10.1111/boc.70018","url":null,"abstract":"<p>Protrusion-derived extracellular vesicles (PD-EVs) are a specialized subset of extracellular vesicles (EVs) generated from dynamic cellular extensions. These structures play a crucial role in cellular communication and have emerged as pivotal mediators in various biological processes, including cancer progression and immune modulation. In cancer, PD-EVs facilitate tumor growth, invasion, and metastasis by delivering oncogenic cargo that remodels the tumor microenvironment, promotes angiogenesis, and supports immune evasion. They are also implicated in establishing pre-metastatic niches and enabling cancer cells to colonize distant organs. PD-EVs are characterized by a distinct molecular signature linked to their origin from specialized plasma membrane domains. Their unique composition makes them promising biomarkers for early cancer detection, disease monitoring, metastatic potential assessment, and therapeutic response evaluation. Targeting PD-EV biogenesis, release, or uptake represents a novel therapeutic strategy to disrupt tumor progression and overcome resistance to current treatments. However, distinguishing PD-EVs from other EV subtypes remains challenging due to overlapping characteristics. This review consolidates the latest evidence on PD-EVs, focusing on their biogenesis, limitations in their study, functional roles in cancer, and potential applications in diagnostics and therapeutics, especially concerning immune modulation and T-cell activation.</p>","PeriodicalId":8859,"journal":{"name":"Biology of the Cell","volume":"117 6","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/boc.70018","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144264509","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Different Cellular Entry Routes for Drug Delivery Using Cell Penetrating Peptides","authors":"Michael Okafor,&nbsp;David Schmitt,&nbsp;Stéphane Ory,&nbsp;Stéphane Gasman,&nbsp;Christelle Hureau,&nbsp;Peter Faller,&nbsp;Nicolas Vitale","doi":"10.1111/boc.70012","DOIUrl":"https://doi.org/10.1111/boc.70012","url":null,"abstract":"<p>The cell plasma membrane acts as a semi-permeable barrier essential for cellular protection and function, posing a challenge for therapeutic molecule delivery. Conventional techniques for crossing this barrier, including biophysical and biochemical methods, often exhibit limitations such as cytotoxicity and the risk of genomic integration when viral vectors are involved. In contrast, cell-penetrating peptides (CPPs) offer a promising non-invasive means to deliver a broad range of molecular cargoes, including proteins, nucleic acids and small molecules, into cells. CPPs, typically 5 to 30 amino acids long and rich in basic or non-polar residues, interact favourably with different cell membranes. These peptides have evolved since the discovery of the HIV-1 TAT peptide in the 1980s, expanding into various CPP families with diverse therapeutic applications. CPPs can form covalent or non-covalent complexes with their cargo, influencing their stability and efficacy. Based on their sequence properties and interactions, CPPs can be amphipathic or non-amphipathic, with distinct mechanisms of membrane penetration, such as direct penetration and endocytosis. While their uptake mechanisms are complex and not fully elucidated, ongoing optimization aims to enhance CPP specificity and efficacy. CPPs have demonstrated potential in drug delivery, gene therapy, cancer treatment and vaccine development, addressing key safety and efficiency concerns associated with viral vectors. This review explores the classification, mechanisms of action and therapeutic potential. It focuses on the intracellular vesicular trafficking of CPPs, highlighting their role as transformative tools in advancing cellular therapies and medical treatments.</p>","PeriodicalId":8859,"journal":{"name":"Biology of the Cell","volume":"117 6","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/boc.70012","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144244266","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}