Article
Multidisciplinary Sciences
Matthew R. Pawlak, Adam T. Smiley, Maria Paz Ramirez, Marcus D. Kelly, Ghaidan A. Shamsan, Sarah M. Anderson, Branden A. Smeester, David A. Largaespada, David J. Odde, Wendy R. Gordon
Summary: Mechanical forces drive critical cellular processes, and the authors present Rupture And Deliver Tension Gauge Tethers (RAD-TGTs) which can record the mechanical history of individual cells by using flow cytometry or sequencing. RAD-TGTs recapitulate prior studies on DNA tension probes and can detect fluorescence gain in the force-generating cell. They can differentiate distinct mechanotypes and have the potential for various applications in combination with CRISPR screens and -omics analysis.
NATURE COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Qiwei Li, Zaozao Chen, Ying Zhang, Shuang Ding, Haibo Ding, Luping Wang, Zhuoying Xie, Yifu Fu, Mengxiao Wei, Shengnan Liu, Jialun Chen, Xuan Wang, Zhongze Gu
Summary: We developed a photonic crystal cellular force microscopy (PCCFM) that enables high-speed, reference-free visualization and quantification of cellular forces. This technology allows real-time monitoring of cellular forces from subcellular to tissue-level scales.
NATURE COMMUNICATIONS
(2023)
Review
Cell Biology
Yasaswi Gayatri Mishra, Bramanandam Manavathi
Summary: Cell-ECM adhesions, with integrins at their core, serve as a crucial link between the cell cytoskeleton and the extracellular matrix, playing a major role in cell signalling for mechanotransduction, migration, proliferation, and other cellular processes. The diverse integrin adhesion complexes, such as focal adhesions and invadosomes, are not only essential for normal cell survival and development, but also play significant roles in various pathological processes.
CELLULAR SIGNALLING
(2021)
Article
Cell Biology
Yuan Wang, Chunlei Zhang, Wenzhong Yang, ShiPeng Shao, Xinmin Xu, Yujie Sun, Pilong Li, Ling Liang, Congying Wu
Summary: This study reveals the important role of LIMD1 as a force-sensitive molecule in FAs, regulating cell movement and migration by organizing and enriching late FA proteins. Furthermore, LIMD1 also plays a critical role in regulating cell spreading, maintaining adhesion dynamics and cellular contractility, as well as in cells' ability to crawl along gradients of substrate stiffness.
DEVELOPMENTAL CELL
(2021)
Article
Biochemical Research Methods
Kailas Shankar Honasoge, Zeynep Karagoz, Benjamin T. Goult, Haguy Wolfenson, Vanessa L. S. LaPointe, Aurelie Carlier
Summary: This study presents a model-based approach to simulate the mechanochemical processes underlying cell-ECM interactions, and proposes that signal-dependent disassembly rate variations play an important role in the regulation of adhesion maturation.
PLOS COMPUTATIONAL BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Ana Lopez-Guajardo, Azeer Zafar, Khairat Al Hennawi, Valentina Rossi, Abdulaziz Alrwaili, Jessica D. Medcalf, Mark Dunning, Niklas Nordgren, Torbjoern Pettersson, Ian D. Estabrook, Rhoda J. Hawkins, Annica K. B. Gad
Summary: The ability of cells to adhere, exert forces, and migrate through their environment is crucial for tissue regeneration and cancer metastasis. This study revealed defects in the forces exerted by transformed and invasive fibroblasts on their environment and cell nucleus, which could be attributed to HDAC6. These findings provide new insights into the role of cellular forces in fibroblasts and their contribution to invasion and metastasis.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2023)
Article
Engineering, Environmental
Zan Zhu, Liang Bao, Dmitry Pestov, Ping Xu, Wei-Ning Wang
Summary: The surface-modulated photocatalyst with a positively charged layer enhances the affinity towards bacterial cells via electrostatic attractions. The experimental results demonstrate that the positively charged layer does promote the contact between bacteria and photocatalyst through electrostatic attractions. The cooperative effects of bacterial cell adhesion and ROS generation significantly enhance the disinfection performance of the photocatalyst.
CHEMICAL ENGINEERING JOURNAL
(2023)
Article
Nanoscience & Nanotechnology
Alexander J. Boys, Roisin M. Owens
Summary: Cellular contraction is a universal phenomenon driving various processes in the body, but measuring cell contractility can be challenging due to the small stresses involved. Bioelectronic devices show promise in overcoming some of the limitations in monitoring cell contraction by providing fast, non-invasive measurements.
Article
Cell Biology
Wei Wang, Yuxuan Zheng, Shuhui Sun, Wei Li, Moshi Song, Qianzhao Ji, Zeming Wu, Zunpeng Liu, Yanling Fan, Feifei Liu, Jingyi Li, Concepcion Rodriguez Esteban, Si Wang, Qi Zhou, Juan Carlos Izpisua Belmonte, Weiqi Zhang, Jing Qu, Fuchou Tang, Guang-Hui Liu
Summary: Understanding the genetic and epigenetic factors of cellular senescence is crucial for developing interventions to slow aging. CRISPR-Cas9-based screens identified genes like KAT7 that alleviate senescence in accelerated aging models, and lentiviral vectors encoding Cas9/sg-Kat7 were effective in alleviating cellular aging and extending lifespan.
SCIENCE TRANSLATIONAL MEDICINE
(2021)
Article
Chemistry, Multidisciplinary
Lei Wang, Dawei Zhang, Zheng-Dong Luo, Pankaj Sharma, Jan Seidel
Summary: This study reports the observation of inhomogeneous friction behavior in copper-deficient CuInP2S6, which exhibits a nanoscale phase separation of polar and non-polar crystalline phases. The phenomenon is attributed to different lattice strains of phases and large strains at the nanoscale phase boundaries, which also manifest in the nonuniform tip-sample adhesion force. The findings provide new insights into nanoscale device design and wear behavior of a phase-separated van der Waals ferroelectric.
ADVANCED FUNCTIONAL MATERIALS
(2023)
Article
Physics, Multidisciplinary
Esteban Vazquez-Hidalgo, Carly M. Farris, Amy C. Rowat, Parag Katira
Summary: Cellular traction forces, dependent on actin-myosin activity, are crucial for developmental and physiological processes. This study presents a unified modeling framework to explain force generation in response to specific conditions. The simulation results show that substrate stiffness and myosin motor quantity contribute to the maximum actin-myosin forces, but bonding dynamics between the cell and substrate are equally important. The force transmitted to the surface per cell-substrate attachment is only a fraction of the maximum force, and traction stress varies with substrate stiffness and myosin motor quantity. Adhesions smaller than 1 μm^2 generate widely variable traction forces, and impulse is a key limitation factor in traction stress.
FRONTIERS IN PHYSICS
(2022)
Article
Engineering, Mechanical
Guangwen Xiao, Bing Wu, Linquan Yao, Quan Shen
Summary: A three-dimensional train-track coupling dynamic model was developed to clarify train-track traction behavior in the low adhesion zone, along with a new anti-slip control algorithm proposed to adjust traction power for maximum utilization of wheel/rail adhesion. Numerical simulation results showed that the traction force would be reduced to achieve maximum admissible force when the anti-slip control algorithm is activated. This model provides a theoretical reference for railway applications in contaminated conditions.
ENGINEERING FAILURE ANALYSIS
(2022)
Article
Hematology
Nam H. K. Nguyen, Roya Rafiee, Abderrahmane Tagmount, Amin Sobh, Alex Loguinov, Angelica K. de Jesus Sosa, Abdelrahman H. Elsayed, Mohammed Gbadamosi, Nathan Seligson, Christopher R. Cogle, Jeffery Rubnitz, Raul Ribeiro, James Downing, Xueyuan Cao, Stanley B. Pounds, Christopher D. Vulpe, Jatinder K. Lamba
Summary: This study utilized CRISPR/Cas9 technology to identify known genes, such as TOP2A and ABCC1, as well as novel genes including RAD54L2, PRKDC, and ZNF451, which may serve as potential therapeutic targets for overcoming treatment resistance.
Article
Cell Biology
Shay Melamed, Shelly Zaffryar-Eilot, Elisabeth Nadjar-Boger, Rohtem Aviram, Huaning Zhao, Wesal Yaseen-Badarne, Rotem Kalev-Altman, Dalit Sela-Donenfeld, Oded Lewinson, Sophie Astrof, Peleg Hasson, Haguy Wolfenson
Summary: This study identifies an enzyme-dependent mechanism that initiates fibronectin fibrillogenesis, independent of force, and plays a critical role in cell adhesion and mechanosensing.
Article
Cell Biology
Nanami Ueda, Masashi Maekawa, Tsubasa S. Matsui, Shinji Deguchi, Tomoyo Takata, Jun Katahira, Shigeki Higashiyama, Miki Hieda
Summary: The linker of nucleoskeleton and cytoskeleton (LINC) complex plays a critical role in regulating cellular structure and signaling during cell migration through traction force. SUN1, a component of the LINC complex, is involved in the maturation of focal adhesions and activation of integrin beta 1, which are both dependent on traction force.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Oncology
Pim Mutsaers, Hayri E. Balcioglu, Rowan Kuiper, Dora Hammerl, Rebecca Wijers, Mark van Duin, Bronno van der Holt, Annemiek Broijl, Walter Gregory, Sonja Zweegman, Pieter Sonneveld, Reno Debets
Summary: Multiple myeloma patients exhibit decreased T-cell immunity, with VISTA expression in the tumor microenvironment correlating significantly with patient survival and T-cell infiltration levels, suggesting VISTA as a potential target for immune therapies.
Article
Oncology
Maud Rijnders, Hayri E. Balcioglu, Debbie G. J. Robbrecht, Astrid A. M. Oostvogels, Rebecca Wijers, Maureen J. B. Aarts, Paul Hamberg, Geert J. L. H. van Leenders, J. Alberto Nakauma-Gonzalez, Jens Voortman, Hans M. Westgeest, Joost L. Boormans, Ronald de Wit, Martijn P. Lolkema, Astrid A. M. van der Veldt, Reno Debets
Summary: This study identified early changes in T-cell subsets that correlate with anti-PD-1 treatment response in patients with metastatic urothelial cancer (mUC). The decrease in the fraction of circulating PD-1(+) CD4(+) T cells and the juxtaposition of Th1 cells with CD8(+) and myeloid cells are associated with treatment response.
CLINICAL CANCER RESEARCH
(2022)
Article
Chemistry, Physical
Hayri E. Balcioglu, Rolf Harkes, Erik H. J. Danen, Thomas Schmidt
Summary: This study used quantitative super-resolution microscopy to investigate cell-matrix adhesions and found that there is a quantitative relationship between cellular traction force and the number of cell-matrix adhesion proteins. The stoichiometry of these proteins changes with different substrate stiffness, indicating a substrate-stiffness-dependent modulation of cell-matrix adhesion.
JOURNAL OF CHEMICAL PHYSICS
(2022)
Article
Oncology
Iris S. C. Verploegh, Andrea Conidi, Rutger W. W. Brouwer, Hayri E. Balcioglu, Panagiotis Karras, Samira Makhzami, Anne Korporaal, Jean-Christophe Marine, Martine Lamfers, Wilfred F. J. van IJcken, Sieger Leenstra, Danny Huylebroeck
Summary: This study characterized the cell viability of patient-derived GBM cultures in response to BMP4 and identified predictive markers for sensitivity to BMP4 using single-cell transcriptome profiling. The changes in composition of GBM cultures after BMP4 treatment correlated with treatment efficacy, with OLIG1/2 expression serving as a predictor and upregulation of RPL27A and RPS27 serving as useful early-response markers.
Article
Biochemistry & Molecular Biology
Chenlin Feng, Xuesong Wang, Willem Jespers, Rongfang Liu, Sofia Denise Zamarbide Losada, Marina Gorostiola Gonzalez, Gerard J. P. van Westen, Erik H. J. Danen, Laura H. Heitman
Summary: This study aims to explore the effects of cancer-patient-derived A(2A)AR mutations on ligand binding and receptor functions. The results show that 6 mutants decrease the binding affinity for agonist NECA, while the V275A mutant increases it. Mutations A165V and A265V also decrease the binding affinity for antagonist ZM241385.
Review
Biochemistry & Molecular Biology
Qiuyu Liu, Victoria A. C. Palmgren, Erik H. J. Danen, Sylvia E. Le Devedec
Summary: Hypoxia is closely linked to therapeutic resistance in breast cancer and can induce an aggressive phenotype conducive to invasion and metastasis. However, there is currently no consensus on the duration of hypoxia and the presence of hypoxia-reoxygenation cycles. This review discusses current methods of hypoxia research, proposes a clear definition of acute, chronic, and intermittent hypoxia, and provides a foundation for in vitro (breast) cancer research related to hypoxia.
MOLECULAR BIOLOGY REPORTS
(2022)
Review
Genetics & Heredity
Yasmin Dekker, Sylvia E. Le Devedec, Erik H. J. Danen, Qiuyu Liu
Summary: This review studies the crosstalk between hypoxia and the extracellular matrix (ECM) in breast cancer. The findings suggest that hypoxia directly contributes to ECM remodeling, alters cell metabolism, and is regulated by the YAP/TAZ mechanotransduction pathway. The review highlights the importance of understanding these interactions for breast cancer progression.
Article
Oncology
Chumut Phanthunane, Rebecca Wijers, Maria J. De Herdt, Senada Koljenovic, Stefan Sleijfer, Robert J. Baatenburg de Jong, Jose Angelito U. Hardillo, Reno Debets, Hayri E. Balcioglu
Summary: In early oral squamous cell carcinoma patients, clusters between CD20 B cells and Tfh cells in the stromal invasive margin are positively associated with patient survival. The close relationship between follicular helper T cells and B cells is closely related to patient prognosis.
Article
Biochemistry & Molecular Biology
Zi Wang, Bircan Coban, Chen-Yi Liao, Yao-Jun Chen, Qiuyu Liu, Erik H. J. Danen
Summary: GRHL2 has different roles in different breast cancer subtypes, promoting cancer growth in some subtypes and suppressing cancer progression in others. Its expression is increased in all subtypes of breast cancer and inversely correlated with overall survival in basal-like breast cancer patients. GRHL2 regulates cell-cell junction, epithelial migration, and proliferation in both luminal and basal A breast cancer subtypes, but has distinct effects on cell cycle arrest and migration in these subtypes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Oncology
Alessandro Gregori, Cecilia Bergonzini, Mjriam Capula, Giulia Mantini, Fatemeh Khojasteh-Leylakoohi, Annalisa Comandatore, Ghazaleh Khalili-Tanha, Alireza Khooei, Luca Morelli, Amir Avan, Erik H. Danen, Thomas Schmidt, Elisa Giovannetti
Summary: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive and chemoresistant cancer, with a stiff stroma surrounding it playing a role in chemoresistance. High expression of the mechanical sensor ITGA2 correlated with a poor prognosis in PDAC patients, and increased matrix stiffness led to the expression of ITGA2 and chemoresistance to gemcitabine. ITGA2 could be a potential therapeutic target to overcome gemcitabine resistance.
Article
Oncology
Qiuyu Liu, Nasi Liu, Vera van der Noord, Wanda van der Stel, Bob van de Water, Erik H. J. Danen, Sylvia E. Le Devedec
Summary: Hypoxia is associated with disease progression and poor prognosis in breast cancer, but little is known about the response of different breast cancer subtypes to hypoxia. This study compared the response of luminal and basal A subtype cell lines to acute and chronic hypoxia. The results showed that both subtypes activate HIF-related pathways, but basal A cells are less affected by hypoxia compared to luminal cells. Notably, hypoxia-induced gene networks were associated with worse survival in breast cancer patients. Different adaptation programs were observed in these subtypes, indicating their contribution to the progression of breast cancer.
BREAST CANCER RESEARCH AND TREATMENT
(2023)
Article
Oncology
Shweta Mahajan, Hayri E. Balcioglu, Astrid Oostvogels, Willem A. Dik, K. C. Allen Chan, Kwok-Wai Lo, Edwin P. Hui, Anna Tsang, Joanna Tong, Wai Kei Jacky Lam, Kenneth Wong, Anthony T. C. Chan, Brigette B. Y. Ma, Reno Debets
Summary: Post-radiotherapy clearance of plasma EBV DNA is associated with prognosis in NPC patients. T cells, particularly CD8+ T cells expressing CCR1, 4 and/or 5, play a role in this clearance process. Differences in chemo-attractants related to T-cell chemotaxis are also linked to clinical outcome. Validation in larger cohorts is needed to confirm these findings.
Article
Cell Biology
Pieter A. A. Roelofs, Mieke A. M. Timmermans, Bojana Stefanovska, Myrthe A. A. den Boestert, Amber W. M. van den Borne, Hayri E. E. Balcioglu, Anita M. M. Trapman, Reuben S. S. Harris, John W. M. Martens, Paul N. N. Span
Summary: APOBEC3B (A3B) is overexpressed in a subset of breast cancers and is associated with advanced disease, poor prognosis, and treatment resistance. The causes of A3B dysregulation in breast cancer remain unclear. In this study, A3B expression levels were quantified in cell lines and breast tumors and related to cell cycle markers. It was found that A3B expression is heterogeneous and strongly associated with the proliferation marker Cyclin B1. Dysregulated A3B overexpression in breast cancer is proposed to be the result of relief from repression and pathway activation during the G(2)/M phase of the cell cycle.
Article
Biochemistry & Molecular Biology
Qiuyu Liu, Wanda van der Stel, Vera E. van der Noord, Hanneke Leegwater, Bircan Coban, Kim Elbertse, Joannes T. M. Pruijs, Olivier J. M. Bequignon, Gerard van Westen, Sylvia E. Le Devedec, Erik H. J. Danen
Summary: Hypoxia triggers HIF1 stabilization in luminal and basal A triple negative breast cancer cells. High throughput targeted RNA sequencing reveals overlapping and distinct target genes being modulated in these subtypes. Hypoxia induces phosphorylation of TAZ at Ser89 in basal A cells, leading to cytoplasmic sequestration of TAZ(Ser89). Hypoxia attenuates growth of basal A cells and diminishes the effect of verteporfin, a disruptor of YAP/TAZ-TEAD-mediated transcription.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)