Biophysics reviews最新文献

Mesoscopic p53-rich clusters represent a new class of protein condensates.

IF 2.9

Biophysics reviews Pub Date : 2025-03-20 eCollection Date: 2025-03-01 DOI: 10.1063/5.0243722

David S Yang, Alexander Tilson, Michael B Sherman, Navin Varadarajan, Peter G Vekilov

{"title":"Mesoscopic p53-rich clusters represent a new class of protein condensates.","authors":"David S Yang, Alexander Tilson, Michael B Sherman, Navin Varadarajan, Peter G Vekilov","doi":"10.1063/5.0243722","DOIUrl":"10.1063/5.0243722","url":null,"abstract":"The protein p53 is an important tumor suppressor, which transforms, after mutation, into a potent cancer promotor. Both mutant and wild-type p53 form amyloid fibrils, and fibrillization is considered one of the pathways of the mutants' oncogenicity. p53 incorporates structured domains, essential to its function, and extensive disordered regions. Here, we address the roles of the ordered (where the vast majority of oncogenic mutations localize) and disordered (implicated in aggregation and condensation of numerous other proteins) domains in p53 aggregation. We show that in the cytosol of model breast cancer cells, the mutant p53 R248Q reproducibly forms fluid aggregates with narrow size distribution centered at approximately 40 nm. Similar aggregates were observed in experiments with purified p53 R248Q, which identified the aggregates as mesoscopic protein-rich clusters, a unique protein condensate. Direct TEM imaging demonstrates that the mesoscopic clusters host and facilitate the nucleation of amyloid fibrils. We show that in solutions of stand-alone ordered domain of WT p53 clusters form and support fibril nucleation, whereas the disordered N-terminus domain forms common dense liquid and no fibrils. These results highlight two unique features of the mesoscopic protein-rich clusters: their role in amyloid fibrillization that may have implications for the oncogenicity of p53 mutants and the defining role of the ordered protein domains in their formation. In a broader context, these findings demonstrate that mutations in the DBD domain, which underlie the loss of cancer-protective transcription function, are also responsible for fibrillization and, thus, the gain of oncogenic function of p53 mutants.","PeriodicalId":72405,"journal":{"name":"Biophysics reviews","volume":"6 1","pages":"011308"},"PeriodicalIF":2.9,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11928095/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143694502","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Sticking together: Polymerization of sickle hemoglobin drives the multiscale pathophysiology of sickle cell disease.

IF 2.9

Biophysics reviews Pub Date : 2025-03-20 eCollection Date: 2025-03-01 DOI: 10.1063/5.0238698

Dillon C Williams, Hannah M Szafraniec, David K Wood

引用次数: 0

Toward universal models for collective interactions in biomolecular condensates.

IF 2.9

Biophysics reviews Pub Date : 2025-03-07 eCollection Date: 2025-03-01 DOI: 10.1063/5.0244227

Edoardo Milanetti, Karan K H Manjunatha, GianCarlo Ruocco, Amos Maritan, Monika Fuxreiter

引用次数: 0

Decoding the effects of mutation on protein interactions using machine learning.

IF 2.9

Biophysics reviews Pub Date : 2025-02-21 eCollection Date: 2025-03-01 DOI: 10.1063/5.0249920

Wang Xu, Anbang Li, Yunjie Zhao, Yunhui Peng

{"title":"Decoding the effects of mutation on protein interactions using machine learning.","authors":"Wang Xu, Anbang Li, Yunjie Zhao, Yunhui Peng","doi":"10.1063/5.0249920","DOIUrl":"10.1063/5.0249920","url":null,"abstract":"Accurately predicting mutation-caused binding free energy changes (ΔΔGs) on protein interactions is crucial for understanding how genetic variations affect interactions between proteins and other biomolecules, such as proteins, DNA/RNA, and ligands, which are vital for regulating numerous biological processes. Developing computational approaches with high accuracy and efficiency is critical for elucidating the mechanisms underlying various diseases, identifying potential biomarkers for early diagnosis, and developing targeted therapies. This review provides a comprehensive overview of recent advancements in predicting the impact of mutations on protein interactions across different interaction types, which are central to understanding biological processes and disease mechanisms, including cancer. We summarize recent progress in predictive approaches, including physicochemical-based, machine learning, and deep learning methods, evaluating the strengths and limitations of each. Additionally, we discuss the challenges related to the limitations of mutational data, including biases, data quality, and dataset size, and explore the difficulties in developing accurate prediction tools for mutation-induced effects on protein interactions. Finally, we discuss future directions for advancing these computational tools, highlighting the capabilities of advancing technologies, such as artificial intelligence to drive significant improvements in mutational effects prediction.","PeriodicalId":72405,"journal":{"name":"Biophysics reviews","volume":"6 1","pages":"011307"},"PeriodicalIF":2.9,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11857871/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143517540","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Decoding chaperone complexes: Insights from NMR spectroscopy. 解码伴侣复合物：来自核磁共振光谱的见解。

IF 2.9

Biophysics reviews Pub Date : 2024-12-10 eCollection Date: 2024-12-01 DOI: 10.1063/5.0233299

Shreya Ghosh, G Marius Clore

{"title":"Decoding chaperone complexes: Insights from NMR spectroscopy.","authors":"Shreya Ghosh, G Marius Clore","doi":"10.1063/5.0233299","DOIUrl":"10.1063/5.0233299","url":null,"abstract":"Molecular chaperones play a key role in protein homeostasis by preventing misfolding and aggregation, assisting in proper protein folding, and sometimes even disaggregating formed aggregates. Chaperones achieve this through a range of transient weak protein-protein interactions, which are difficult to study using traditional structural and biophysical techniques. Nuclear magnetic resonance (NMR) spectroscopy, however, is well-suited for studying such dynamic states and interactions. A wide range of NMR experiments have been particularly valuable in understanding the mechanisms of chaperone function, as they can characterize disordered protein structures, detect weak and nonspecific interactions involving sparsely populated states, and probe the conformational dynamics of proteins and their complexes. Recent advances in NMR have significantly enhanced our knowledge of chaperone mechanisms, especially chaperone-client interactions, despite the inherent challenges posed by the flexibility and complexity of these systems. In this review, we highlight contributions of NMR to the chaperone field, focusing on the work carried out in our laboratory, which have provided insights into how chaperones maintain function within the cellular environment and interact with various protein substrates.","PeriodicalId":72405,"journal":{"name":"Biophysics reviews","volume":"5 4","pages":"041308"},"PeriodicalIF":2.9,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11637561/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142831116","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Regulation of cytoskeleton dynamics and its interplay with force in plant cells. 植物细胞的细胞骨架动力学调控及其与力的相互作用

IF 2.9

Biophysics reviews Pub Date : 2024-11-25 eCollection Date: 2024-12-01 DOI: 10.1063/5.0201899

Zhenping Sun, Xueqing Wang, Chaoyong Peng, Liufeng Dai, Ting Wang, Yi Zhang

引用次数: 0

Spatially defined microenvironment for engineering organoids. 空间限定的有机体工程微环境

IF 2.9

Biophysics reviews Pub Date : 2024-10-18 eCollection Date: 2024-12-01 DOI: 10.1063/5.0198848

Yilan Zhang, Fukang Qi, Peng Chen, Bi-Feng Liu, Yiwei Li

{"title":"Spatially defined microenvironment for engineering organoids.","authors":"Yilan Zhang, Fukang Qi, Peng Chen, Bi-Feng Liu, Yiwei Li","doi":"10.1063/5.0198848","DOIUrl":"10.1063/5.0198848","url":null,"abstract":"In the intricately defined spatial microenvironment, a single fertilized egg remarkably develops into a conserved and well-organized multicellular organism. This observation leads us to hypothesize that stem cells or other seed cell types have the potential to construct fully structured and functional tissues or organs, provided the spatial cues are appropriately configured. Current organoid technology, however, largely depends on spontaneous growth and self-organization, lacking systematic guided intervention. As a result, the structures replicated in vitro often emerge in a disordered and sparse manner during growth phases. Although existing organoids have made significant contributions in many aspects, such as advancing our understanding of development and pathogenesis, aiding personalized drug selection, as well as expediting drug development, their potential in creating large-scale implantable tissue or organ constructs, and constructing multicomponent microphysiological systems, together with functioning at metabolic levels remains underutilized. Recent discoveries have demonstrated that the spatial definition of growth factors not only induces directional growth and migration of organoids but also leads to the formation of assembloids with multiple regional identities. This opens new avenues for the innovative engineering of higher-order organoids. Concurrently, the spatial organization of other microenvironmental cues, such as physical stresses, mechanical loads, and material composition, has been minimally explored. This review delves into the burgeoning field of organoid engineering with a focus on potential spatial microenvironmental control. It offers insight into the molecular principles, expected outcomes, and potential applications, envisioning a future perspective in this domain.","PeriodicalId":72405,"journal":{"name":"Biophysics reviews","volume":"5 4","pages":"041302"},"PeriodicalIF":2.9,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11646138/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142831118","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Regulation of epithelial cell jamming transition by cytoskeleton and cell-cell interactions. 细胞骨架和细胞间相互作用对上皮细胞干扰转换的调控。

IF 2.9

Biophysics reviews Pub Date : 2024-10-14 eCollection Date: 2024-12-01 DOI: 10.1063/5.0220088

Zoe D Latham, Alexandra Bermudez, Jimmy K Hu, Neil Y C Lin

{"title":"Regulation of epithelial cell jamming transition by cytoskeleton and cell-cell interactions.","authors":"Zoe D Latham, Alexandra Bermudez, Jimmy K Hu, Neil Y C Lin","doi":"10.1063/5.0220088","DOIUrl":"10.1063/5.0220088","url":null,"abstract":"Multicellular systems, such as epithelial cell collectives, undergo transitions similar to those in inert physical systems like sand piles and foams. To remodel or maintain tissue organization during development or disease, these collectives transition between fluid-like and solid-like states, undergoing jamming or unjamming transitions. While these transitions share principles with physical systems, understanding their regulation and implications in cell biology is challenging. Although cell jamming and unjamming follow physics principles described by the jamming diagram, they are fundamentally biological processes. In this review, we explore how cellular processes and interactions regulate jamming and unjamming transitions. We begin with an overview of how these transitions control tissue remodeling in epithelial model systems and describe recent findings of the physical principles governing tissue solidification and fluidization. We then explore the mechanistic pathways that modulate the jamming phase diagram axes, focusing on the regulation of cell fluctuations and geometric compatibility. Drawing upon seminal works in cell biology, we discuss the roles of cytoskeleton and cell-cell adhesion in controlling cell motility and geometry. This comprehensive view illustrates the molecular control of cell jamming and unjamming, crucial for tissue remodeling in various biological contexts.","PeriodicalId":72405,"journal":{"name":"Biophysics reviews","volume":"5 4","pages":"041301"},"PeriodicalIF":2.9,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11479637/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142482225","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Capturing the illusive ring-shaped intermediates in Aβ42 amyloid formation. 捕捉 Aβ42 淀粉样蛋白形成过程中虚幻的环形中间体

IF 2.9

Biophysics reviews Pub Date : 2024-08-13 eCollection Date: 2024-09-01 DOI: 10.1063/5.0222349

Yu Yuan, Xiaozhe Dong, Huan Wang, Feng Gai

引用次数: 0

Decoding physical principles of cell migration under controlled environment using microfluidics. 利用微流体技术解码细胞在受控环境下迁移的物理原理。

IF 2.9

Biophysics reviews Pub Date : 2024-07-29 eCollection Date: 2024-09-01 DOI: 10.1063/5.0199161

Young Joon Suh, Alan T Li, Mrinal Pandey, Cassidy S Nordmann, Yu Ling Huang, Mingming Wu

{"title":"Decoding physical principles of cell migration under controlled environment using microfluidics.","authors":"Young Joon Suh, Alan T Li, Mrinal Pandey, Cassidy S Nordmann, Yu Ling Huang, Mingming Wu","doi":"10.1063/5.0199161","DOIUrl":"10.1063/5.0199161","url":null,"abstract":"Living cells can perform incredible tasks that man-made micro/nano-sized robots have not yet been able to accomplish. One example is that white blood cells can sense and move to the site of pathogen attack within minutes. The robustness and precision of cellular functions have been perfected through billions of years of evolution. In this context, we ask the question whether cells follow a set of physical principles to sense, adapt, and migrate. Microfluidics has emerged as an enabling technology for recreating well-defined cellular environment for cell migration studies, and its ability to follow single cell dynamics allows for the results to be amenable for theoretical modeling. In this review, we focus on the development of microfluidic platforms for recreating cellular biophysical (e.g., mechanical stress) and biochemical (e.g., nutrients and cytokines) environments for cell migration studies in 3D. We summarize the basic principles that cells (including bacteria, algal, and mammalian cells) use to respond to chemical gradients learned from microfluidic systems. We also discuss about novel biological insights gained from studies of cell migration under biophysical cues and the need for further quantitative studies of cell function under well-controlled biophysical environments in the future.","PeriodicalId":72405,"journal":{"name":"Biophysics reviews","volume":"5 3","pages":"031302"},"PeriodicalIF":2.9,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11290890/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141876856","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0