Article
Optics
Kevin Affannoukoue, Simon Labouesse, Guillaume Maire, Laurent Gallais, Julien Savatier, Marc Allain, Md Rasedujjaman, Loic Legoff, Jerome Idier, Renaud Poincloux, Florence Pelletier, Christophe Leterrier, Thomas Mangeat, Anne Sentenac
Summary: A benefit of random illumination microscopy (RIM) is that it improves the resolution and linearity of structured illumination microscopy using speckled illumination. In this study, RIM was implemented in the TIRF configuration for imaging biological processes close to the coverslip surface, achieving high-resolution images on fixed samples and dynamic images on live macrophages. The simplicity of the experimental setup and imaging protocol, as well as the robustness of the data processing, make TIRF-RIM a preferred method for super-resolution TIRF imaging.
Article
Optics
Zetao Fan, Yan Kuai, Xi Tang, Yifan Zhang, Douguo Zhang
Summary: This paper proposes a novel TIRF microscope based on a photonic chip, which can replace conventional objectives or prisms for simplified optical configuration and shadowless illumination.
Article
Nanoscience & Nanotechnology
Grant Ashby, Kayla E. Keng, Carl C. Hayden, Sadhana Gollapudi, Justin R. Houser, Sabah Jamal, Jeanne C. Stachowiak
Summary: Cell surface receptors are actively recycled by endocytosis, and their differential expression makes them targets for drug-carrier particles. The size of liposomes, rather than the density of ligands on their surfaces, primarily determines their probability of uptake. Targeting has the greatest impact on endocytosis of liposomes of intermediate diameters.
ACS APPLIED MATERIALS & INTERFACES
(2023)
Article
Cell Biology
Ying Zhang, Jing Zhu, Hao Xu, Qin Yi, Liang Yan, Liang Ye, Xinyuan Zhang, Min Xie, Bin Tan
Summary: Using real-time confocal microscopy and structured illumination microscopy, we observed the time-dependent internalization of fluorescently labeled S100B protein (S100B-Alexa488) into MSCs and its transport through endolysosomal pathways. Inhibitors and RNA interference approaches further demonstrated that clathrin and lipid rafts play important roles in the internalization of S100B-Alexa488, providing potential interventions for the safe application of MSCs in glioma therapy.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Biology
Sarina Veit, Laura Charlotte Paweletz, Soren S-R Bohr, Anant K. Menon, Nikos S. Hatzakis, Thomas Guenther Pomorski
Summary: Reconstitution of membrane proteins into model membranes is crucial for functional analysis, but existing model-membrane systems have limitations in sample heterogeneity and insufficient knowledge of lipid and protein content. This study presents a new microscopy-based bleaching protocol that allows parallel analysis of multiple parameters of individual proteoliposomes prepared with fluorescently tagged membrane proteins and lipid markers.
Review
Neurosciences
Kate L. Prichard, Nicholas S. O'Brien, Sari R. Murcia, Jennifer R. Baker, Adam McCluskey
Summary: Endocytosis is a crucial process for cell health and signaling, specifically clathrin mediated endocytosis (CME) plays a key role in synaptic vesicle recycling and intracellular communication in the brain. This review focuses on clathrin and dynamin, two proteins involved in CME, and discusses the potential therapeutic interventions and inhibitors for conditions involving defects in CME.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Sarah M. Smith, Gabrielle Larocque, Katherine M. Wood, Kyle L. Morris, Alan M. Roseman, Richard B. Sessions, Stephen J. Royle, Corinne J. Smith
Summary: The interaction between Clathrin and the AP2 complex plays a crucial role in coated-pit assembly, with a beta 2 appendage able to bind in at least two positions in the clathrin cage. This multi-modal binding is shown to be a fundamental property of clathrin-AP2 interactions.
Article
Multidisciplinary Sciences
Alan M. Szalai, Bruno Siarry, Jeronimo Lukin, David J. Williamson, Nicolas Unsain, Alfredo Caceres, Mauricio Pilo-Pais, Guillermo Acuna, Damian Refojo, Dylan M. Owen, Sabrina Simoncelli, Fernando D. Stefani
Summary: The photometric method SIMPLER allows decoding of the axial position of single molecules in a total internal reflection fluorescence microscope without hardware modification, delivering nearly isotropic nanometric resolution 3D images in single-molecule localization microscopy. Achieving high axial resolution remains challenging in this field.
NATURE COMMUNICATIONS
(2021)
Article
Chemistry, Analytical
Teliang Zhang, Xueliang Wang, Youjun Zeng, Songfeng Huang, Xiaoqi Dai, Weifu Kong, Qian Liu, Jiajie Chen, Junle Qu, Yonghong Shao
Summary: Surface plasmon resonance microscopy (SPRM) is widely used in biological fields for its high spatial resolution and label-free detection. In this study, a home-built SPRM system based on total internal reflection (TIR) was utilized to study the imaging of a single nanoparticle. By using a ring filter and deconvolution algorithm, the parabolic tail of the nanoparticle image was removed, achieving a spatial resolution of 248 nm. Additionally, specific binding between human IgG antigen and goat anti-human IgG antibody was successfully measured using TIR-based SPRM, demonstrating its capability in imaging sparse nanoparticles and monitoring biomolecular interactions.
Article
Chemistry, Analytical
Haechang Yang, Sanghoon Shin, Dongmin Seo, Jaewon Park, Sungkyu Seo
Summary: This study introduces an optical method for fast and accurate PM analysis, utilizing total internal reflection technology to achieve high-contrast microscopic images. The proposed method shows superior signal-to-noise ratios compared to traditional methods and enhances detection capabilities for microbeads and ultrafine particles. The side-illuminated TIR PM detection device holds significant advantages over other systems due to its detection capability, simplicity, compactness, and low cost.
Article
Biochemistry & Molecular Biology
Alexander Johnson, Walter A. Kaufmann, Christoph Sommer, Tommaso Costanzo, Dana A. Dahhan, Sebastian Y. Bednarek, Jiri Friml
Summary: Biological systems are made up of dynamic three-dimensional parts. This study introduces novel methods to analyze biological structures and focuses on Arabidopsis clathrin-coated vesicles (CCVs). The methods allow for visualization of CCVs in unroofed cells and biochemical isolated organelles at high resolution, and also provide a deep learning analysis method for screening CCVs in metal replicated samples.
Article
Biochemistry & Molecular Biology
Annabelle Tan, Zain Ahmad, Pete Vukusic, Joao T. Cabral
Summary: We investigate the combined effects of surface diffraction and total internal reflection in the design of 3-dimensional materials exhibiting distinct structural colour on various facets. We propose a simple model that can account for all experimental observations. Using polydimethylsiloxane (PDMS), we demonstrate that multifaceted colours can respond to their environment. By coupling a right angle triangular prism with a surface grating, we demonstrate the straightforward fabrication of a GRISM. Finally, we outline possibilities for predictive material design using multi-axial wrinkling patterns and more complex polyhedra.
Article
Biochemistry & Molecular Biology
Ahmet Ata Akatay, Tianyao Wu, Umidahan Djakbarova, Cristopher Thompson, Emanuele Cocucci, Roya Zandi, Joseph Rudnick, Comert Kural
Summary: This study investigates the formation of clathrin coats using various microscopy techniques. In addition to the known pits and plaques, the formation of giant coated pits (GCPs) is reported for the first time. It is found that increased membrane tension induces the formation of GCPs, which then split into smaller fragments during internalization.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2022)
Article
Biology
Xingyu Zhang, Li Zou, Lanxia Meng, Min Xiong, Lina Pan, Guiqin Chen, Yongfa Zheng, Jing Xiong, Zhihao Wang, Duc M. Duong, Zhaohui Zhang, Xuebing Cao, Tao Wang, Li Tang, Keqiang Ye, Zhentao Zhang
Summary: Amphiphysin I plays a crucial role in Alzheimer's disease, mediating tau hyperphosphorylation and synaptic dysfunction. Cleavage of Amphiphysin I by AEP leads to detrimental effects in the molecular mechanisms involved.
Article
Polymer Science
J. Alejandro Rivera-Moran, Peter R. Lang
Summary: This paper investigates the influence of noise effects, particle size, and sampling time on total internal reflection microscopy (TIRM) measurement results. It finds that detector shot noise and prolonged sampling times may cause erroneous results in steep parts of the interaction potential, while background noise has negligible effects. Noise does not significantly affect dynamic data, but lengthy sampling times and small probe particle radii can cause issues. Additionally, the study observes that dynamic results may differ from standard hydrodynamic predictions due to partial slip.
Article
Biology
Cristina Olivieri, Caitlin Walker, Adak Karamafrooz, Yingjie Wang, V. S. Manu, Fernando Porcelli, Donald K. Blumenthal, David D. Thomas, David A. Bernlohr, Simon M. Sandford, Susan S. Taylor, Gianluigi Veglia
Summary: The fusion of the dynamic J-domain to PKA-C disrupts the internal allosteric network, causing attenuation of nucleotide/PKI binding cooperativity. This reduced allosteric cooperativity alters specific recognitions and interactions between substrates and regulatory partners, contributing to dysregulation exhibited by PKA-C-DNAJB1.
COMMUNICATIONS BIOLOGY
(2021)
Article
Pathology
Daniel J. Rowan, Saba Yasir, Zongming E. Chen, Taofic Mounajjed, Sibel Erdogan Damgard, Lisa Cummins, Lizhi Zhang, Emma Whitcomb, Vince Falck, Sanford M. Simon, Aatur D. Singhi, Michael S. Torbenson
Summary: Myxoid hepatic adenomas are a rare subtype of hepatic adenomas that predominantly occur in older individuals and have an elevated risk of malignant transformation. They are characterized by the combined inactivation of HNF1A and additional mutations that cluster in the PKA pathway.
AMERICAN JOURNAL OF SURGICAL PATHOLOGY
(2021)
Article
Oncology
Gadi Lalazar, David Requena, Lavoisier Ramos-Espiritu, Denise Ng, Patrick D. Bhola, Ype P. de Jong, Ruisi Wang, Nicole J. C. Narayan, Bassem Shebl, Solomon Levin, Eleftherios Michailidis, Mohammad Kabbani, Koen O. A. Vercauteren, Arlene M. Hurley, Benjamin A. Farber, William J. Hammond, James A. Saltsman, Ethan M. Weinberg, J. Fraser Glickman, Barbara A. Lyons, Jessica Ellison, Erik Schadde, Martin Hertl, Jennifer L. Leiting, Mark J. Truty, Rory L. Smoot, Faith Tierney, Tomoaki Kato, Hans-Guido Wendel, Michael P. LaQuaglia, Charles M. Rice, Anthony Letai, Philip Coffino, Michael S. Torbenson, Michael Ortiz, Sanford M. Simon
Summary: Therapeutics informed by genomics have not been effective for fibrolamellar carcinoma (FLC). A functional drug screen identified that inhibitors of TOPO1 and HDAC, along with napabucasin, showed efficacy on patient-derived xenografts (PDX) of FLC. Inhibiting Bcl-xL in combination with these drugs also showed synergy in treating FLC.
Article
Biochemistry & Molecular Biology
Tejeshwar C. Rao, Reena R. Beggs, Katherine E. Ankenbauer, Jihye Hwang, Victor Pui-Yan Ma, Khalid Salaita, Susan L. Bellis, Alexa L. Mattheyses
Summary: This study explores the influence of heterogeneity within the glycocalyx on cell adhesion mechanics and signaling. Specifically, it investigates the role of specific glycosylation subtypes, such as the addition of sialic acid to terminal glycans, in altering receptor function and regulating cell mechanics. The researchers found that high activity of the sialyltransferase ST6Gal-I promotes increased integrin forces and spreading in cancer cells, and these phenotypes are EGFR-specific. They also discovered that different aspects of cell mechanics, such as tension, contractility, adhesion, spreading, proliferation, and invasion, are regulated by different signaling pathways. Additionally, the study demonstrates that high ST6Gal-I activity leads to sustained EGFR membrane retention, highlighting its importance as a key regulator of cell mechanics and motility.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Medicine, Research & Experimental
Reena R. Beggs, Tejeshwar C. Rao, William F. Dean, Andrew P. Kowalczyk, Alexa L. Mattheyses
Summary: The study revealed structural rearrangements in desmosomes during maturation, with some parts of desmoplakin showing decreased plaque-to-plaque distance and increased plaque length, while other parts remained constant. This structural reorganization was correlated with desmosome maturation and adhesive strength, suggesting that the architectural organization of desmosomes can indicate their maturation state. Additionally, migrating cells showed differences in desmosome structure compared to those forming at the wound edge, highlighting the impact of cell migration on desmosome assembly and architecture.
Article
Multidisciplinary Sciences
Tomasz J. Nawara, Yancey D. Williams, Tejeshwar C. Rao, Yuesong Hu, Elizabeth Sztul, Khalid Salaita, Alexa L. Mattheyses
Summary: By utilizing STAR microscopy, researchers quantified the nanoscale dynamics of clathrin-coat shape change during vesicle assembly, revealing multiple productive mechanisms of vesicle formation and advocating for the flexible model of CME.
NATURE COMMUNICATIONS
(2022)
Article
Cell & Tissue Engineering
Nicole J. C. Narayan, David Requena, Gadi Lalazar, Lavoisier Ramos-Espiritu, Denise Ng, Solomon Levin, Bassem Shebl, Ruisi Wang, William J. Hammond, James A. Saltsman III, Helmuth Gehart, Michael S. Torbenson, Hans Clevers, Michael P. LaQuaglia, Sanford M. Simon
Summary: In this study, patient-derived organoids were successfully developed and used as a model system to recapitulate the histologic morphology, immunohistochemistry, and transcriptome of fibrolamellar carcinoma (FLC). This model system shows promise for improving our understanding of this rare cancer and for drug testing and development.
Article
Biophysics
William F. Dean, Alexa L. Mattheyses
Summary: This study investigates the architecture of desmosomal cadherins (DCs) and their role in cell adhesion through fluorescence microscopy. The results show significant structural differences between the extracellular and intracellular domains of DCs, with extracellular adhesive interactions playing a predominant role in their organization.
BIOPHYSICAL JOURNAL
(2022)
Article
Oncology
Christoph Neumayer, Denise Ng, Caroline S. Jiang, Adam Qureshi, Gadi Lalazar, Roger Vaughan, Sanford M. Simon
Summary: The fusion gene DNAJB1-PRKACA is found to be a recurrent mutation in fibrolamellar hepatocellular carcinoma (FLC). Continued expression of DNAJB1-PRKACA is essential for tumor growth and its inhibition can lead to cell death. This discovery has implications for investigating other fusion genes in pediatric cancers and advancing precision therapies.
CLINICAL CANCER RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Xiao Wang, Sanford M. Simon, Philip Coffino
Summary: This study used single molecule experiments to measure the dwell time of substrates interacting with the AAA+ ATPase unfoldase/translocase ClpX, finding that tail length and composition of the substrates affect substrate retention during futile unfolding. Both polyG and GAr have inhibitory effects on unfolding, but act differently.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Medicine, Research & Experimental
Bassem Shebl, Denise Ng, Gadi Lalazar, Carly Rosemore, Tova M. Finkelstein, Rachael D. Migler, Guangrong Zheng, Peiyi Zhang, Caroline S. Jiang, Adam Qureshi, Roger Vaughan, Mark Yarchoan, Ype P. de Jong, Charles M. Rice, Philip Coffino, Michael V. Ortiz, Daohong Zhou, Sanford M. Simon
Summary: Fibrolamellar hepatocellular carcinoma (FLC) is a rare and lethal liver cancer with no effective systemic therapy. Inhibiting the antiapoptotic protein BCL-XL has shown synergy with various systemic therapies for FLC cells in vitro. However, the physiological expression of BCL-XL in platelets has hindered previous attempts to target this vulnerability in other cancers.
Article
Biophysics
Tomasz J. Nawara, William F. Dean, Alexa L. Mattheyses
Summary: Protein interactions with the plasma membrane play a crucial role in cell viability, but our understanding of how key proteins sense or induce unfavorable membrane shapes is limited. STAR microscopy provides high-resolution imaging of protein dynamics at the plasma membrane, but data processing is time-consuming. To address this, we present DrSTAR, a user-friendly MATLAB-based package that improves data processing efficiency, allowing for the study of nanometer-scale changes in protein distribution.
BIOPHYSICAL JOURNAL
(2023)
Correction
Oncology
Sanford M. Simon
NATURE REVIEWS CANCER
(2023)
Review
Oncology
Sanford M. Simon
Summary: The fight against rare cancers is challenged by issues such as misdiagnosis, lack of information and tools, limited samples, and inadequate funding. However, studying rare cancers has led to important discoveries in cancer biology, such as the identification of tumor suppressor genes. Fibrolamellar hepatocellular carcinoma (FLC) is a rare and difficult-to-diagnose liver cancer that primarily affects young individuals. Through a personal journey, Sanford Simon shares insights into whether FLC is a single cancer type or a collection of similar phenotypes, and its genetic inheritance or somatic mutation origins.
NATURE REVIEWS CANCER
(2023)
Article
Gastroenterology & Hepatology
Amichai Berkovitz, Rachael D. Migler, Adam Qureshi, Carly Rosemore, Michael S. Torbenson, Roger Vaughan, Erin Marcotte, Sanford M. Simon
Summary: Fibrolamellar hepatocellular carcinoma (FLC) is a rare primary liver cancer primarily affecting adolescents and young adults. Female gender is associated with improved survival, while the presence of 10 or more tumors within the liver and metastases at diagnosis are associated with worse survival. This study utilized a patient community-based FLC registry to highlight the importance of rare tumor registries in advancing clinical and scientific discoveries.
HEPATOLOGY COMMUNICATIONS
(2022)