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A Mechanometabolism Toolbox for Studying Cell Migration. 研究细胞迁移的机械代谢工具箱。
IF 8.4 2区 生物学
Cold Spring Harbor perspectives in biology Pub Date : 2025-09-22 DOI: 10.1101/cshperspect.a041755
Katherine M Young, Santiago Lopez, Keefer Boone, Mehmet Acikel, Xavi Gallart, Cynthia Reinhart-King
{"title":"A Mechanometabolism Toolbox for Studying Cell Migration.","authors":"Katherine M Young, Santiago Lopez, Keefer Boone, Mehmet Acikel, Xavi Gallart, Cynthia Reinhart-King","doi":"10.1101/cshperspect.a041755","DOIUrl":"https://doi.org/10.1101/cshperspect.a041755","url":null,"abstract":"<p><p>Cell migration is greatly affected by both the physical properties of the motile cell itself and the environment through which the cell is moving. In addition to studying cellular and extracellular mechanical properties in the context of cell migration, there is a growing interest in understanding the intersection between migration, mechanics, and metabolism. In this work, we discuss the many techniques and approaches researchers are currently using to study cellular mechanics, extracellular mechanics, and metabolism in the context of cell migration. Our goal is to bring exposure to new approaches in the fields of mechanobiology and mechanometabolism and highlight the importance of studying cell migration through a mechanical lens.</p>","PeriodicalId":10494,"journal":{"name":"Cold Spring Harbor perspectives in biology","volume":" ","pages":""},"PeriodicalIF":8.4,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145124255","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The Unusual Effectiveness of Evolution in Systems Neuroscience. 进化在系统神经科学中的不同寻常的有效性。
IF 8.4 2区 生物学
Cold Spring Harbor perspectives in biology Pub Date : 2025-09-22 DOI: 10.1101/cshperspect.a041510
Arkarup Banerjee, Steven M Phelps, Justus M Kebschull
{"title":"The Unusual Effectiveness of Evolution in Systems Neuroscience.","authors":"Arkarup Banerjee, Steven M Phelps, Justus M Kebschull","doi":"10.1101/cshperspect.a041510","DOIUrl":"https://doi.org/10.1101/cshperspect.a041510","url":null,"abstract":"<p><p>This perspective advocates for \"evolutionary systems neuroscience\" as a framework combining evolutionary biology with neural circuit analysis. Evolution creates natural circuit modifications that preserve essential functions while enabling new behaviors. Modern technologies now allow researchers to investigate causal connections from genes to circuits to behaviors with unprecedented precision. By studying both convergent and divergent evolution, we can uncover both broad computational principles and specific implementation mechanisms. Across diverse examples-from insect courtship to rodent communication-we explore how targeted circuit changes drive behavioral innovation without disrupting core functions. This framework may reveal \"deep homologies\" in neural mechanisms, similar to how evolutionary developmental biology (evo-devo) identified conserved genetic toolkits in morphological development. This evolutionary lens promises not just to reveal how brains work, but why they work the way they do-providing insights that extend beyond neuroscience to complex adaptive systems more broadly.</p>","PeriodicalId":10494,"journal":{"name":"Cold Spring Harbor perspectives in biology","volume":" ","pages":""},"PeriodicalIF":8.4,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145124287","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
From Signals to Protrusions: Modeling Excitable Systems in Cell Migration. 从信号到突起：细胞迁移中可兴奋系统的建模。
IF 8.4 2区 生物学
Cold Spring Harbor perspectives in biology Pub Date : 2025-09-22 DOI: 10.1101/cshperspect.a041746
Pablo A Iglesias, Parijat Banerjee
{"title":"From Signals to Protrusions: Modeling Excitable Systems in Cell Migration.","authors":"Pablo A Iglesias, Parijat Banerjee","doi":"10.1101/cshperspect.a041746","DOIUrl":"https://doi.org/10.1101/cshperspect.a041746","url":null,"abstract":"<p><p>Cell migration is a fundamental biological process critical for development, immune response, and wound healing, but its dysregulation contributes to pathological conditions such as cancer metastasis. Recent research has demonstrated that migration is driven by excitable signal transduction and cytoskeletal networks, which function as separate but coupled systems. The signal transduction excitable network (STEN) propagates excitatory signals, while the cytoskeletal excitable network (CEN) generates cytoskeletal protrusions. Although distinct, these networks interact dynamically: STEN regulates CEN, while CEN provides feedback to STEN, influencing cell polarization and directionality. Computational models incorporating nonlinear dynamics and reaction-diffusion systems have successfully recapitulated these interactions, shedding light on their role in pseudopod formation, chemotaxis, and mechanosensation. This review discusses recent experimental and theoretical advances, highlighting how excitable systems underlie cell motility and how mathematical modeling helps to understand their role.</p>","PeriodicalId":10494,"journal":{"name":"Cold Spring Harbor perspectives in biology","volume":" ","pages":""},"PeriodicalIF":8.4,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145124340","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Chemical and Mechanical Regulation of Leukocyte Migration. 白细胞迁移的化学和机械调控。
IF 8.4 2区 生物学
Cold Spring Harbor perspectives in biology Pub Date : 2025-09-22 DOI: 10.1101/cshperspect.a041752
Jonathan H Schrope, Tanner F Robertson, Milka Sarris, Anna Huttenlocher
{"title":"Chemical and Mechanical Regulation of Leukocyte Migration.","authors":"Jonathan H Schrope, Tanner F Robertson, Milka Sarris, Anna Huttenlocher","doi":"10.1101/cshperspect.a041752","DOIUrl":"https://doi.org/10.1101/cshperspect.a041752","url":null,"abstract":"<p><p>Directed leukocyte motility is essential for immunity and host defense. Dysregulated leukocyte migration is implicated in clinical immunodeficiency and hyperinflammatory conditions. Leukocytes sense both chemical and physical cues within the environment to regulate internal migration machinery and thus coordinate the immune response and its resolution. In response to environmental cues, leukocytes cater migration strategies to both exert forces on surrounding tissues and alter the chemical environment through self-generated gradients. Here, we synthesize recent advances in our understanding of how chemical and physical cues within the tissue environment regulate leukocyte motility, with implications to develop therapeutic strategies to modulate the immune response in human disease.</p>","PeriodicalId":10494,"journal":{"name":"Cold Spring Harbor perspectives in biology","volume":" ","pages":""},"PeriodicalIF":8.4,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145124187","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Collective Cell Migration Strategies: Patterning, Motility, and Directionality of the Posterior Lateral Line Primordium in Zebrafish. 集体细胞迁移策略：斑马鱼后侧线原基的模式、运动性和方向性。
IF 8.4 2区 生物学
Cold Spring Harbor perspectives in biology Pub Date : 2025-09-22 DOI: 10.1101/cshperspect.a041751
Alex V Nechiporuk, Holger Knaut
{"title":"Collective Cell Migration Strategies: Patterning, Motility, and Directionality of the Posterior Lateral Line Primordium in Zebrafish.","authors":"Alex V Nechiporuk, Holger Knaut","doi":"10.1101/cshperspect.a041751","DOIUrl":"https://doi.org/10.1101/cshperspect.a041751","url":null,"abstract":"<p><p>During development and homeostasis, tissues move and rearrange to form organs, seal wounds, or-in the case of cancer-spread in the body. To accomplish this, cells in tissues need to communicate with each other, generate force to push themselves forward, and know where to go to-all of this with little to no error. Here, we discuss how a migrating tissue-the zebrafish posterior lateral line primordium-solves these challenges. We focus on the strategies that ensure signaling within the tissue, enable the tissue to generate and transmit force to its substrate for propulsion, and allow robust directional sensing and migration by the tissue. These strategies include facilitated diffusion and ligand trapping for focal signaling, a self-generated attractant gradient for long-distance migration, clamping of the attractant concentration to the attractant receptor's <i>K</i> <sub><i>d</i></sub> for most sensitive signaling, mechanical coupling among cells for averaging directional sensing in a tissue, and large rear traction stresses to propel the tissue forward. Many of these strategies likely apply to collectively migrating cells in other contexts and should thus provide insights with direct relevance to human health.</p>","PeriodicalId":10494,"journal":{"name":"Cold Spring Harbor perspectives in biology","volume":" ","pages":""},"PeriodicalIF":8.4,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145124260","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Ca2+ Fluxes across Membrane Contact Sites. 钙离子在膜接触部位的通量。
IF 8.4 2区 生物学
Cold Spring Harbor perspectives in biology Pub Date : 2025-09-09 DOI: 10.1101/cshperspect.a041765
Lucia Barazzuol, Marisa Brini, Tito Calì
{"title":"Ca<sup>2+</sup> Fluxes across Membrane Contact Sites.","authors":"Lucia Barazzuol, Marisa Brini, Tito Calì","doi":"10.1101/cshperspect.a041765","DOIUrl":"https://doi.org/10.1101/cshperspect.a041765","url":null,"abstract":"<p><p>The calcium ion (Ca<sup>2+</sup>) is a pivotal second messenger orchestrating diverse cellular functions, including metabolism, signaling, and apoptosis. Membrane contact sites (MCSs) are critical hubs for Ca<sup>2+</sup> exchange, enabling rapid and localized signaling across cell compartments. Well-characterized interfaces, such as those between the endoplasmic reticulum (ER) and mitochondria and ER-plasma membrane (PM), mediate Ca<sup>2+</sup> flux through specialized channels. Less understood, yet significant, contacts involving Golgi, lysosomes, peroxisomes, and the nucleus further expand the landscape of intracellular Ca<sup>2+</sup> signaling. These organelles are engaged in Ca<sup>2+</sup> homeostasis mainly through their MCS, but the molecular players and the mechanisms regulating the process of Ca<sup>2+</sup> transfer remain incompletely elucidated. This review provides a comprehensive overview of Ca<sup>2+</sup> signaling across diverse MCS, emphasizing understudied organelles and the need for further investigation to uncover novel therapeutic opportunities.</p>","PeriodicalId":10494,"journal":{"name":"Cold Spring Harbor perspectives in biology","volume":" ","pages":""},"PeriodicalIF":8.4,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145029054","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Leading the Way: Molecular Drivers of Single-Cell Migration. 引领道路：单细胞迁移的分子驱动。
IF 8.4 2区 生物学
Cold Spring Harbor perspectives in biology Pub Date : 2025-09-02 DOI: 10.1101/cshperspect.a041748
Dong Li, Hui Tu, Huaqing Cai
{"title":"Leading the Way: Molecular Drivers of Single-Cell Migration.","authors":"Dong Li, Hui Tu, Huaqing Cai","doi":"10.1101/cshperspect.a041748","DOIUrl":"10.1101/cshperspect.a041748","url":null,"abstract":"<p><p>Cell migration plays a central role in a wide range of physiological, developmental, and disease-related processes. Studies using single-cell models, such as <i>Dictyostelium discoideum</i>, have provided important insights into the molecular principles underlying this process. Migrating cells exhibit a polarized morphology, with actin-rich protrusions at the leading edge driving forward motion and an actomyosin network at the trailing edge enabling retraction. While actin polymerization and direct cytoskeletal regulators are essential, a complex network of signaling molecules also play a critical role in cell migration. Initially viewed as part of the directional sensing machinery in guided migration, this signaling network is now also recognized as an integral component of the motility module itself. Its spontaneous activity coordinates with cytoskeletal reorganization, enabling cell migration even in the absence of external cues. This review highlights key cytoskeletal and signaling molecules involved in leading-edge protrusion formation, with an emphasis on findings from <i>Dictyostelium</i> studies. We also discuss recent advances in understanding how these cytoskeletal and signaling molecules organize into excitable networks to regulate cell motility.</p>","PeriodicalId":10494,"journal":{"name":"Cold Spring Harbor perspectives in biology","volume":" ","pages":""},"PeriodicalIF":8.4,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12401055/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144526728","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Telomeres and Human Disease. 端粒与人类疾病
IF 8.4 2区 生物学
Cold Spring Harbor perspectives in biology Pub Date : 2025-09-02 DOI: 10.1101/cshperspect.a041684
Sharon A Savage
{"title":"Telomeres and Human Disease.","authors":"Sharon A Savage","doi":"10.1101/cshperspect.a041684","DOIUrl":"10.1101/cshperspect.a041684","url":null,"abstract":"<p><p>Telomeres, the long nucleotide repeats, and protein complex at chromosome ends, are central to genomic integrity. Telomere length (TL) varies widely between populations due to germline genetics, environmental exposures, and other factors. Very short telomeres caused by pathogenic germline variants in telomere maintenance genes cause the telomere biology disorders, a spectrum of life-threatening conditions including bone marrow failure, liver and lung disease, cancer, and other complications. Cancer predisposition with long telomeres is caused by rare pathogenic germline variants in components of the shelterin telomere protection protein complex and associated primarily with elevated risk of melanoma, thyroid cancer, sarcoma, and lymphoproliferative malignancies. In the middle, studies of the general population at risk of common illnesses, such as cardiovascular disease and cancer, have found statistically significant differences in TL but uncertain clinical applicability. This work reviews connections between telomere biology and human disease focusing on similarities and differences across the phenotypic spectrum.</p>","PeriodicalId":10494,"journal":{"name":"Cold Spring Harbor perspectives in biology","volume":" ","pages":""},"PeriodicalIF":8.4,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12401058/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143647567","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Plant Breeding and the Origins of Genetics. 植物育种与遗传学的起源。
IF 8.4 2区 生物学
Cold Spring Harbor perspectives in biology Pub Date : 2025-09-02 DOI: 10.1101/cshperspect.a041714
Nils Roll-Hansen
{"title":"Plant Breeding and the Origins of Genetics.","authors":"Nils Roll-Hansen","doi":"10.1101/cshperspect.a041714","DOIUrl":"10.1101/cshperspect.a041714","url":null,"abstract":"<p><p>This paper argues that the historiography of genetics ∼1900, the formation period of modern science, is too narrow. It lacks attention to plant breeding. Perhaps this omission also narrows the present understanding of fundamental ideas like the genotype/phenotype distinction and the gene concept? There is a mythical story still told in textbooks and at anniversaries: As modern genetics started with the rediscovery of Mendel's laws in 1900, a fateful controversy over continuous or discontinuous variation of heredity between biometricians and Mendelians. Discontinuity appeared as a threat to the Darwinian theory of evolution by natural selection. Only by the 1920s was the problem solved by a theory of population genetics founded on the chromosome theory of heredity.<sup>1</sup> However, in plant breeding ∼1900 ideas of heredity and evolution were closely intertwined, and the combination of discontinuous heredity with continuous Darwinian evolution was an obvious option.</p>","PeriodicalId":10494,"journal":{"name":"Cold Spring Harbor perspectives in biology","volume":" ","pages":""},"PeriodicalIF":8.4,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12401043/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142715550","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Calcium Signaling and Metabolic Reprogramming in Cancer: Mechanisms and Therapeutic Implications. 癌症中的钙信号和代谢重编程：机制和治疗意义。
IF 8.4 2区 生物学
Cold Spring Harbor perspectives in biology Pub Date : 2025-08-18 DOI: 10.1101/cshperspect.a041764
Evan Courmont, Anna Rita Cantelmo
{"title":"Calcium Signaling and Metabolic Reprogramming in Cancer: Mechanisms and Therapeutic Implications.","authors":"Evan Courmont, Anna Rita Cantelmo","doi":"10.1101/cshperspect.a041764","DOIUrl":"10.1101/cshperspect.a041764","url":null,"abstract":"<p><p>Calcium is essential for cellular homeostasis, orchestrating a vast array of physiological processes through tightly regulated storage, flux, and signaling pathways. Dysregulation of calcium homeostasis disrupts these finely tuned processes, leading to aberrant signaling that contributes to cancer progression. Beyond its role in cellular dysfunction, calcium also regulates the metabolic reprogramming in cancer cells, enabling them to adapt their metabolism to support tumor growth, survival, and resistance. Despite its fundamental role, direct therapeutic targeting of calcium signaling in cancer remains elusive. This review explores the intricate cross talk between calcium signaling and cancer metabolism, dissecting how distinct calcium dynamics drive adaptive oncogenic adaptations. Deciphering this interplay may reveal therapeutic opportunities that leverage calcium-dependent metabolic vulnerabilities in cancer. Given its broad influence, calcium signaling regulation could serve as a multitargeting strategy for anticancer therapy, broadening the range of potential therapeutic interventions.</p>","PeriodicalId":10494,"journal":{"name":"Cold Spring Harbor perspectives in biology","volume":" ","pages":""},"PeriodicalIF":8.4,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144871797","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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