Article
Biochemistry & Molecular Biology
Noe Quittot, Mathilde Fortier, Margaryta Babych, Phuong Trang Nguyen, Mathew Sebastiao, Steve Bourgault
Summary: The study reveals that GAGs exacerbate IAPP-induced cytotoxicity and membrane perturbation, increasing the local concentration of IAPP on the cell surface and promoting lipid bilayer disturbance and cell death.
Article
Biochemistry & Molecular Biology
Mathilde Fortier, Melanie Cote-Cyr, Vy Nguyen, Margaryta Babych, Phuong Trang Nguyen, Roger Gaudreault, Steve Bourgault
Summary: This study investigates the physicochemical and conformational properties driving the self-assembly of islet amyloid polypeptide (IAPP) and its associated cytotoxicity. It reveals the importance of the 12-17 hydrophobic region for self-recognition and identifies certain amino acids critical for amyloid fibril formation. Additionally, the study shows that modulating the peptide backbone flexibility at position Leu16 can inhibit amyloid formation and reduce cytotoxicity. These findings contribute to the development of therapeutic approaches for preventing IAPP aggregation.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Giovanna Lucia Delogu, Benedetta Era, Sonia Floris, Rosaria Medda, Valeria Sogos, Francesca Pintus, Gianluca Gatto, Amit Kumar, Gunilla Torstensdotter Westermark, Antonella Fais
Summary: The study found that hydroxylated 2-phenylbenzofurans compounds exhibited strong inhibitory activity against alpha-glucosidase, with compound 16 showing the best performance. It also effectively inhibited IAPP aggregation without significant cytotoxicity.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2021)
Article
Biochemistry & Molecular Biology
Lucie Khemtemourian, Hebah Fatafta, Benoit Davion, Sophie Lecomte, Sabine Castano, Birgit Strodel
Summary: This study investigates the molecular details of IAPP binding to lipid membranes, revealing different membrane interaction modes and aggregation structures for different IAPP variants. Residue 18 plays a decisive role in the structure and membrane interaction of IAPP, making it a potential therapeutic target for inhibiting IAPP toxicity.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2022)
Article
Multidisciplinary Sciences
Christin Pohl, Gregory Effantin, Eaazhisai Kandiah, Sebastian Meier, Guanghong Zeng, Werner Streicher, Dorotea Raventos Segura, Per H. Mygind, Dorthe Sandvang, Line Anker Nielsen, Gunther H. J. Peters, Guy Schoehn, Christoph Mueller-Dieckmann, Allan Noergaard, Pernille Harris
Summary: This study reports the cryo-EM structure of a triple-mutant of the antimicrobial peptide plectasin, which assembles into helical non-amyloid fibrils. The fibril formation is reversible and pH- and concentration-dependent. This finding reveals that alpha/beta proteins can naturally assemble into fibrils.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Ye Wang, Joakim Bergstrom, Martin Ingelsson, Gunilla T. T. Westermark
Summary: This study investigates the interaction between alpha-synuclein (aSyn) and islet amyloid polypeptide (IAPP) in Alzheimer's disease and type 2 diabetes. The results show intracellular co-localization of aSyn with IAPP, but aSyn is absent in the extracellular amyloid deposits. In vitro experiments demonstrate that preformed aSyn fibrils can seed IAPP fibril formation, but IAPP does not affect aSyn fibrillation.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Ming-Hao Li, Xiaoxue Zhang, Erwin London, Daniel P. Raleigh
Summary: Human islet amyloid polypeptide (hIAPP) plays a role in regulating glucose levels but forms pancreatic amyloid in type-2 diabetes. The concentration of anionic lipids in 13-cell plasma membrane is low. Ca2+ and Mg2+ affect hIAPP-membrane interactions by neutralizing POPS charge.
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
(2023)
Review
Cell Biology
Sofia Ferreira, Ana F. Raimundo, Regina Menezes, Ivo C. Martins
Summary: This study discusses the association of IAPP with diabetes, Aβ, and dementia, elucidating the pathological role of IAPP in AD. Research has shown that IAPP not only contributes to cognitive decline, but also harms the blood-brain barrier, interacts directly with Aβ, and co-deposits with it, leading to diabetes-associated dementia.
NEURAL REGENERATION RESEARCH
(2021)
Article
Endocrinology & Metabolism
Joseph J. Castillo, Alfred C. Aplin, Daryl J. Hackney, Meghan F. Hogan, Nathalie Esser, Andrew T. Templin, Rehana Akter, Steven E. Kahn, Daniel P. Raleigh, Sakeneh Zraika, Rebecca L. Hull
Summary: The study found that aggregation of IAPP is toxic to islet endothelial cells and induces inflammatory responses, resulting in decreased capillary density, increased capillary diameter, and an increased number of pericytes.
Review
Cell Biology
Angelina S. Bortoletto, Ronald J. Parchem
Summary: Patients with type 2 diabetes mellitus have a significantly higher risk of developing dementia, possibly due to increased secretion of amylin. This review summarizes the mechanisms by which amylin accumulation may cause neuronal damage and discusses the importance of investigating new therapeutic targets for treating dementia.
NEURAL REGENERATION RESEARCH
(2023)
Review
Cell Biology
Carine Marmentini, Renato C. S. Branco, Antonio C. Boschero, Mirian A. Kurauti
Summary: Islet amyloid polypeptide is a hormone co-secreted with insulin by pancreatic beta-cells and is found in patients with type 2 diabetes. Investigating aspects related to amyloid formation is crucial for developing strategies towards beta-cell protection. Approaches to prevent islet amyloid cytotoxicity have shown promise in improving beta-cell function and preventing hyperglycemia.
JOURNAL OF CELLULAR PHYSIOLOGY
(2022)
Article
Endocrinology & Metabolism
Austin J. Taylor, Evgeniy Panzhinskiy, Paul C. Orban, Francis C. Lynn, David F. Schaeffer, James D. Johnson, Janel L. Kopp, C. Bruce Verchere
Summary: Loss of IAPP signaling may not increase the risk of pancreatic cancer in individuals with diabetes.
MOLECULAR METABOLISM
(2022)
Article
Medicine, Research & Experimental
Luiz E. M. Cardoso, Thatiany Souza Marinho, Fabiane Ferreira Martins, Marcia Barbosa Aguila, Carlos A. Mandarim-de-Lacerda
Summary: In this study, the effects of a glucagon-like peptide type 1 receptor agonist, semaglutide, on the turnover of islet extracellular matrix (ECM) components in an obese mouse model were investigated. The results showed that semaglutide improved the turnover of ECM components and reduced the formation of amyloid deposits.
Article
Multidisciplinary Sciences
Yingna Xu, Wenbo Feng, Qingtong Zhou, Anyi Liang, Jie Li, Antao Dai, Fenghui Zhao, Jiahui Yan, Chuan-Wei Chen, Hao Li, Li-Hua Zhao, Tian Xia, Yi Jiang, H. Eric Xu, Dehua Yang, Ming-Wei Wang
Summary: This study reports the cryo-electron microscopy structure of human VIP2R bound to its endogenous ligand PACAP27 and the stimulatory G protein, revealing a unique interaction mode between PACAP27 and the receptor stabilized by the N-terminal alpha-helix of VIP2R. Truncation or extension of VIP2R significantly decreases VIP2R-mediated cAMP accumulation.
NATURE COMMUNICATIONS
(2022)
Article
Dentistry, Oral Surgery & Medicine
Yiyi Huang, Tingyu Wang, Yucong Chen, Huancai Lin, Dongru Chen
Summary: This study selected the most stable amyloid hexapeptide GIDLKI (GI6) to inhibit biofilm formation by multiple species of bacteria, including the cariogenic bacterium Streptococcus mutans. The results showed that GI6 effectively prevented and alleviated the development of dental caries without adverse effects on other organs in the body.
JOURNAL OF DENTISTRY
(2023)
Article
Multidisciplinary Sciences
Lior Pytowski, Chiu Fan Lee, Alex C. Foley, David J. Vaux, Letitia Jean
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2020)
Article
Physics, Multidisciplinary
Leiming Chen, Chiu Fan Lee, John Toner
PHYSICAL REVIEW LETTERS
(2020)
Article
Physics, Multidisciplinary
David Nesbitt, Gunnar Pruessner, Chiu Fan Lee
Summary: The dynamics of dry active matter have important implications for a range of biological phenomena, including animal flocking, cell tissue dynamics, and swarming of insects and bacteria. Many interesting behaviors have been observed at high densities, but remain difficult to simulate due to computational demand. By modifying the lattice Boltzmann method, researchers were able to study two-dimensional dry active fluids in a dense regime, uncovering multiple novel phase transitions and supporting simulation results with analytical treatment of hydrodynamic equations.
NEW JOURNAL OF PHYSICS
(2021)
Article
Multidisciplinary Sciences
Andrew W. Folkmann, Andrea Putnam, Chiu Fan Lee, Geraldine Seydoux
Summary: This study reveals that the dynamics of biomolecular condensates are regulated by protein clusters. Through experiments and theory, it is demonstrated that the assembly of P granules is controlled by MEG-3 protein, which helps lower surface tension and slow down coarsening.
Article
Physics, Multidisciplinary
Chiu Fan Lee
Summary: Motility-induced phase separation (MIPS) is a non-equilibrium phenomenon where self-propelled particles separate into different phases without attractive interactions. It is characterized by the emergence of polar, nematic, and higher order structures at the interface, which are poorly understood. By using a model that captures all many-body interactions through effective speed and pressure functions dependent on local particle density, the study derives an infinite set of integral formulas for the ordering structures at the interface. It is shown that half of these formulas are exact for generic active Brownian particle systems and validated through numerical simulations.
NEW JOURNAL OF PHYSICS
(2022)
Article
Physics, Multidisciplinary
Andrew Killeen, Thibault Bertrand, Chiu Fan Lee
Summary: A collection of motile cells, each generating contractile nematic stresses in isolation, can exhibit extensile nematic behavior at the tissue level, which seems contradictory. Understanding this phenomenon is crucial in biology and has fundamental significance in soft matter and many body physics.
PHYSICAL REVIEW LETTERS
(2022)
Article
Physics, Multidisciplinary
Leiming Chen, Chiu Fan Lee, Ananyo Maitra, John Toner
Summary: We present a hydrodynamic theory of incompressible polar active fluids with quenched random field disorder, showing that despite the disruption caused by the disorder, these fluids can move coherently with a non-zero mean velocity in the hydrodynamic limit. However, linearized hydrodynamics cannot describe the scaling behavior of this class of active systems in spatial dimensions between 2 and 5. Nevertheless, we obtained exact dimension-dependent scaling exponents in these dimensions.
PHYSICAL REVIEW LETTERS
(2022)
Article
Physics, Multidisciplinary
Leiming Chen, Chiu Fan Lee, Ananyo Maitra, John Toner
Summary: This study investigates the ordered phase of incompressible polar active fluids in the presence of quenched disorder in two dimensions. The research reveals the robustness of the ordered state and provides scaling laws. The findings have significant implications for understanding the coherent motion of biological systems.
PHYSICAL REVIEW LETTERS
(2022)
Article
Multidisciplinary Sciences
Benjamin Partridge, Sara Gonzalez Anton, Reema Khorshed, George Adams, Constandina Pospori, Cristina Lo Celso, Chiu Fan Lee
Summary: Multi-potent progenitor cells play a key role in hematopoiesis by migrating in and out of different niches to determine their fate. Our analysis of experimental data and the use of a cell motion model revealed that these cells display transient super-diffusion, highlighting the importance of motility in early hematopoietic progenitor function.
Article
Physics, Multidisciplinary
Patrick Jentsch, Chiu Fan Lee
Summary: Active matter is a fertile ground for novel physics, and dynamic renormalization group (DRG) analysis has revealed many new universality classes in polar active fluids (PAFs). However, previous studies have been limited due to technical difficulties, and only explored compressible PAFs at the one-loop level. In this study, we use functional renormalization group (FRG) methods to overcome these limitations and uncover critical behavior in compressible PAFs, calculating critical exponents beyond the one-loop level. We find three universality classes, and show that at least two of these classes violate the fluctuation-dissipation relation, indicating they are out of equilibrium.
PHYSICAL REVIEW RESEARCH
(2023)
Article
Multidisciplinary Sciences
Andrea Cairoli, Alice Spenlehauer, Darryl R. Overby, Chiu Fan Lee
Summary: Cells can adapt to hostile environmental conditions by dynamically changing their shape. Scientists propose that the formation of giant vacuoles can be described as inverse blebbing and model this process to explain it.
Article
Physics, Fluids & Plasmas
Leiming Chen, Chiu Fan Lee, Ananyo Maitra, John Toner
Summary: We study the moving phase of two-dimensional incompressible polar active fluids in the presence of both quenched and annealed disorder. We show that long-range polar order persists in this defect-ridden two-dimensional system. By employing three distinct dynamic renormalization group schemes, we obtain the scaling laws of velocity fluctuations at large distances and long times. Surprisingly, the quenched and annealed parts of the velocity correlation function exhibit the same anisotropy exponent and the relaxational and propagating parts of the dispersion relation have the same dynamic exponent in the nonlinear theory, despite being distinct in the linearized theory. This is attributed to anomalous hydrodynamics. Furthermore, the three renormalization schemes yield similar universal exponents, indicating the high accuracy of the numerical values predicted.
Article
Physics, Multidisciplinary
Thibault Bertrand, Chiu Fan Lee
Summary: By using generic hydrodynamic equations, we unify various phase transitions and phase coexistences in active fluids and identify a new coexistence phase and a multicritical point.
PHYSICAL REVIEW RESEARCH
(2022)
Article
Physics, Multidisciplinary
Chiu Fan Lee
Summary: Phase separation is a common phenomenon in various physical systems and biological cells. Recent experimental studies have found that the coarsening rates of intracellular condensates are unexpectedly slow, possibly due to the slow conversion of condensate constituents. Traditional theories of phase separation are no longer applicable, but the conversion-limited phase separation model can be mapped onto a grain growth model in three-dimensional materials.
PHYSICAL REVIEW RESEARCH
(2021)