Article
Medicine, General & Internal
Arkadiusz Lepucki, Kinga Orlinska, Aleksandra Mielczarek-Palacz, Jacek Kabut, Pawel Olczyk, Katarzyna Komosinska-Vassev
Summary: The extracellular matrix is a dynamic molecular network composed of various molecules that play a critical role in regulating cell-cell and cell-matrix interactions, influencing cell growth, migration, and differentiation, as well as serving as a reservoir for cytokines and growth factors. The breakdown of normal ECM and its replacement with tumor ECM is a key driver for tumorigenesis and metastasis, affecting the composition of the tumor microenvironment and promoting malignant progression. Abnormal ECM also affects stromal cells, tumor-associated angiogenesis, inflammation, and the immune response. Understanding the role of ECM in breast cancer can help identify disease markers and therapeutic targets.
JOURNAL OF CLINICAL MEDICINE
(2022)
Review
Biotechnology & Applied Microbiology
Victor Alfonso Solarte David, Viviana Raquel Guiza-Argueello, Martha L. Arango-Rodriguez, Claudia L. Sossa, Silvia M. Becerra-Bayona
Summary: The absence or damage of tissue is a major cause of diseases, and novel therapeutic alternatives aim to recover lost functions through tissue regeneration. Chronic cutaneous lesions are common wounds that require regenerative medicine and tissue engineering interventions to develop bioactive medical products for proper healing and prevention of complications. The coordination of cells, extracellular matrix (ECM), and biomolecules is crucial in tissue repair and regeneration, with ECM acting as a biological platform for their interactions. Tissue engineering utilizes synthetic polymers and decellularized tissues to mimic native ECM and provide necessary functionalities for cell differentiation.
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Katie Trinh, Sohel M. Julovi, Natasha M. Rogers
Summary: The extracellular matrix and ECM-regulatory proteins play crucial roles in cardiac development, organ remodeling, and injury repair. They possess diverse functionality regulated by multiple structural domains and interactions with extracellular substrates and/or cell surface receptors. Various cell types within the myocardium produce ECM proteins, and their importance in cardiovascular physiology and pathology has been increasingly recognized. Understanding the contribution of ECM to cardiovascular disease provides potential pharmacological targets for cardiac diseases and beyond.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Clinical Neurology
Jonathan Larochelle, Changjun Yang, Lei Liu, Eduardo Candelario-Jalil
Summary: Poststroke infections are common complications of stroke and have a negative impact on patient outcomes. Stroke-induced immunosuppression and autonomic signaling alterations make the body more susceptible to both external (nosocomial/community-acquired) and internal (commensal bacterial) infections. Poststroke gut permeability and gut dysbiosis play a crucial role in the hypothesis of commensal infection. Dysregulation of matrix metalloproteinase-7 (MMP-7) production may be critical in the progression of gut permeability after stroke.
Review
Biochemistry & Molecular Biology
Lokender Kumar, Monish Bisen, Azhar Khan, Pradeep Kumar, Sanjay Kumar Singh Patel
Summary: This review discusses the role of MMPs in skeletal muscle function, muscle injury and repair, as well as the potential applications of MMPs in the treatment of musculoskeletal disorders.
Review
Engineering, Biomedical
Chaitanya Tondepu, Lohitash Karumbaiah
Summary: Glioblastoma (GBM) is a highly invasive type of cancer with a dismal survival rate, where current treatments targeting cancer cells fail to consider the significant role of the tumor microenvironment. Research suggests that aberrantly modified glycans in the tumor microenvironment play a crucial role in tumor progression and therapeutic resistance, indicating the potential for developing alternative strategies targeting glycans to improve treatment efficacy.
ADVANCED HEALTHCARE MATERIALS
(2022)
Article
Neurosciences
Martina Chmelova, Peter Androvic, Denisa Kirdajova, Jana Tureckova, Jan Kriska, Lukas Valihrach, Miroslava Anderova, Lydia Vargova
Summary: This study reveals the relationship between age-related extracellular matrix (ECM) modifications and the pathology and outcomes of ischemic stroke in the brain. Genes encoding proteins related to ECM degradation were found to be more active in aged mice, while other ECM molecules also showed significant upregulation. Additionally, genes associated with the protective function of ECM were downregulated after ischemia. Proteins related to neuroinflammation and neurodegeneration were also found to be overexpressed, particularly in aged post-ischemic animals.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2023)
Article
Biochemistry & Molecular Biology
Carson C. Cole, Mikita Misiura, Sarah A. H. Hulgan, Caroline M. Peterson, Joseph W. Williams III, Anatoly B. Kolomeisky, Jeffrey D. Hartgerink
Summary: Cation-pi interactions play a significant role in stabilizing globular proteins, but their role in collagen triple helices is not well understood. This study investigates the effects of pairwise amino acid interactions between cationic and aromatic residues in both axial and lateral relationships.
Review
Biochemistry & Molecular Biology
Umberto Bracale, Roberto Peltrini, Biancamaria Iacone, Mirko Martirani, Daniele Sannino, Antonio Gargiulo, Francesco Corcione, Raffaele Serra, Umberto Marcello Bracale
Summary: This study aimed to investigate the relationship between extracellular matrix disorders and abdominal wall hernias (AWHs) and the levels of matrix metalloproteinases (MMPs). The results showed that AWHs may be a disease of the extracellular matrix, supported by increased levels of MMPs in patients with AWHs. The study also highlighted the impact of tissue inhibitors of metalloproteinases (TIMPs) on AWHs. More prospective studies are needed to confirm the relationship between these biomarkers and the risk of AWHs.
Article
Biochemistry & Molecular Biology
Fabian Graf, Patrick Horn, Anthony D. Ho, Michael Boutros, Christian Maercker
Summary: This study found that mesenchymal stromal cells from human bone marrow may induce migratory activity in cancer cells, and extracellular matrix proteins could be potential drivers of cancer cell migration. Knocking down the gene encoding beta 1 integrin led to inhibition of cancer cell migration, suggesting that integrin signaling plays a crucial role in metastasis.
Article
Engineering, Biomedical
Heejeong Yoon, Jeong Kon Seo, Tae-Eun Park
Summary: A new in vitro tool called adipose tissue microphysiological system (MPS) has been developed to mimic the pathophysiology of adipose tissue in obesity, providing valuable insights into the development of obesity-related disorders.
ACTA BIOMATERIALIA
(2023)
Review
Dentistry, Oral Surgery & Medicine
Erison Santana dos Santos, Joab Cabral Ramos, Ana Luiza Oliveira Correa Roza, Bruno Augusto Linhares Almeida Mariz, Adriana Franco Paes Leme
Summary: Osteopontin (OPN) is a calcium-binding glycol-phosphoprotein that is involved in various physiological and pathological processes, including oral cancer. Its activation of the PI3K/AKT/mTOR pathway contributes to the malignant phenotype of cancer cells, leading to cell proliferation, invasion, metastasis, angiogenesis, and resistance to treatment. Further research is needed to fully understand the role of OPN in oral cancer.
Article
Genetics & Heredity
Prarthana Gopinath, Aparna Natarajan, Amritha Sathyanarayanan, Sridevi Veluswami, Gopal Gopisetty
Summary: The extracellular matrix (ECM) is composed of various proteins, proteoglycans, growth factors, and other components, forming the tumor microenvironment. The proteins in ECM, including adhesive proteins and matricellular proteins (MCP), play significant roles in tumorigenesis, therapeutic resistance, and metastasis. This review focuses on multiple ECM proteins and their contributions to tumor initiation, growth, invasion, and therapeutic resistance, as well as their potential as biomarkers and therapeutic targets.
Review
Cell Biology
Lisa Mazeas, Rina Yonamine, Tristan Barbeyron, Bernard Henrissat, Elodie Drula, Nicolas Terrapon, Chikako Nagasato, Cecile Herve
Summary: In brown algae, the extracellular matrix (ECM) and its polymers have important roles in growth and development. This review provides an overview of ECM construction in brown algae, including its chemical composition and structural model. It discusses the assembly and synthesis of key polysaccharides, and proposes future investigations at the cellular and biochemical levels.
SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Tonia K. Tsinman, Xi Jiang, Lin Han, Eiki Koyama, Robert L. Mauck, Nathaniel A. Dyment
Summary: The study tracks the growth of the meniscus in mice from embryonic formation through the first month of growth, revealing that matrix and cellular features defining specific tissue zones are present at birth and further refined with postnatal growth. This work establishes a detailed timeline of spatiotemporal changes at both the cellular and matrix level during meniscus maturation, providing insight into mechanisms of tissue degeneration and regenerative strategies.
Article
Biochemistry & Molecular Biology
Sepehr Dehghani-Ghahnaviyeh, Karan Kapoor, Emad Tajkhorshid
Summary: This study used molecular dynamics simulations to investigate the ATP hydrolysis-induced conformational changes in Pgp nucleotide-binding domains (NBDs), revealing that ATP/ADP exchange induced conformational changes within the conserved signature motif of NBDs, resulting in relative orientational changes. Furthermore, putative hydrolysis-competent configurations were captured, with a conserved glutamate in the Walker-B motif acting as a catalytic base capturing a water molecule likely initiating ATP hydrolysis.
Article
Biophysics
Defne Gorgun, Muyun Lihan, Karan Kapoor, Emad Tajkhorshid
Summary: This study investigated the interaction between SARS-CoV2 FP and mammalian cellular membranes using molecular dynamics simulations, demonstrating that FP can deeply penetrate into the membrane and form stable bindings. Based on clustering analysis, it was proposed that the most deeply inserted membrane-bound form may represent the biologically relevant form more closely.
BIOPHYSICAL JOURNAL
(2021)
Editorial Material
Chemistry, Physical
Charles L. Brooks, David A. Case, Steve Plimpton, Benoit Roux, David van der Spoel, Emad Tajkhorshid
JOURNAL OF CHEMICAL PHYSICS
(2021)
Article
Multidisciplinary Sciences
Ichia Chen, Shashank Pant, Qianyi Wu, Rosemary J. Cater, Meghna Sobti, Robert J. Vandenberg, Alastair G. Stewart, Emad Tajkhorshid, Josep Font, Renae M. Ryan
Summary: Glutamate is an important excitatory neurotransmitter in the central nervous system, and its proper control is crucial for normal brain function. Recent research has revealed that glutamate transporters can form an aqueous cavity during the transport cycle, allowing for chloride ion conduction. This discovery provides insight into the mechanism by which these transporters support their dual function.
Article
Multidisciplinary Sciences
William R. Arnold, Lauren N. Carnevale, Zili Xie, Javier L. Baylon, Emad Tajkhorshid, Hongzhen Hu, Aditi Das
Summary: Endocannabinoids formed by epoxidation reciprocally modulate canabinoid receptors and display anti-inflammatory activity.
NATURE COMMUNICATIONS
(2021)
Article
Engineering, Biomedical
Ali Rasouli, Yousef Jamali, Emad Tajkhorshid, Omid Bavi, Hossein Nejat Pishkenari
Summary: This study investigates the mechanical properties of ester- and ether-DPhPC lipid bilayers using molecular dynamics simulation. It reveals that ether bilayers are stiffer, less ordered, and thicker compared to ester bilayers, with the presence of ether linkage decreasing the area per lipid in the ether lipid bilayer. The computational framework highlights how ether modification impacts the mechano-chemical properties of DPhPC bilayers.
JOURNAL OF THE MECHANICAL BEHAVIOR OF BIOMEDICAL MATERIALS
(2021)
Article
Biochemistry & Molecular Biology
Hannah C. Huff, Archit Vasan, Pritam Roy, Aayush Kaul, Emad Tajkhorshid, Aditi Das
Summary: Cytochrome P450 2D6 (CYP2D6) interacts with phytocannabinoids in a polymorphism-specific and class-specific manner.
Article
Biochemistry & Molecular Biology
Jingpeng Ge, Johannes Elferich, Sepehr Dehghani-Ghahnaviyeh, Zhiyu Zhao, Marc Meadows, Henrique von Gersdorff, Emad Tajkhorshid, Eric Gouaux
Summary: This study demonstrates how prestin in outer hair cells mediates signal amplification by coupling conformational changes to alterations in membrane surface area. Cryo-EM structures and computational studies reveal the allosteric coupling between the anion site and changes in the transmembrane domain and surrounding membrane. These findings provide insight into the electromotility of outer hair cells.
Article
Chemistry, Multidisciplinary
Liang Sun, Hong-Jun Cho, Soumyo Sen, Andres S. Arango, Truc T. Huynh, Yiran Huang, Nilantha Bandara, Buck E. Rogers, Emad Tajkhorshid, Liviu M. Mirica
Summary: The development of the novel amphiphilic compound LS-4 significantly increases the binding affinity for various Aβ peptide aggregates, showing therapeutic potential for 5xFAD mice. The compound can penetrate the blood-brain barrier, reduce amyloid plaques and phosphorylated tau aggregates, and modulate microglia activation.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Article
Oncology
Christopher G. Mayne, Weiyi Toy, Kathryn E. Carlson, Trusha Bhatt, Sean W. Fanning, Geoffrey L. Greene, Benita S. Katzenellenbogen, Sarat Chandarlapaty, John A. Katzenellenbogen, Emad Tajkhorshid
Summary: By utilizing advanced computational techniques rooted in molecular dynamics simulations, this study characterizes the molecular mechanisms by which specific acquired somatic point mutations lead to constitutive activation of the estrogen receptor. The research identifies how activating mutations affect the structure and function of the ER ligand-binding domain, providing insights into resistance mechanisms in breast cancer.
MOLECULAR CANCER RESEARCH
(2021)
Article
Multidisciplinary Sciences
Zhaleh Ghaemi, Martin Gruebele, Emad Tajkhorshid
Summary: The disassembly process of HBV capsid involves structurally heterogeneous cracks mainly within hexameric sites, with only a small subset of capsid protein monomers engaged in each instance of disassembly. Specific residues at interfaces between dimers within hexamers, such as R127, I139, Y132, N136, A137, and V149, are identified as hot spots for disassembly by avoiding overstabilization of capsids, and are evolutionarily conserved.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Biology
Nandan Haloi, Po-Chao Wen, Qunli Cheng, Meiying Yang, Gayathri Natarajan, Amadou Ks Camara, Wai-Meng Kwok, Emad Tajkhorshid
Summary: The study elucidates the process of complex formation between HKII and VDAC1, confirming a partial blockade of the VDAC1 channel in the complex and the disruptive effect of VDAC1 phosphorylation on HKII binding.
COMMUNICATIONS BIOLOGY
(2021)
Article
Biology
Shashank Pant, Jiaren Zhang, Eung Chang Kim, Kin Lam, Hee Jung Chung, Emad Tajkhorshid
Summary: Research using molecular dynamics simulations and electrophysiology has revealed the allosteric role of phosphatidylinositol-4,5-bisphosphate (PIP2) in the activation of K(v)7.2 channels, influencing protein conformation and correlated motions.
COMMUNICATIONS BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Janina Sprenger, Anda Trifan, Neal Patel, Ashley Vanderbeck, Jenny Bredfelt, Emad Tajkhorshid, Roger Rowlett, Leila Lo Leggio, Karin S. Akerfeldt, Sara Linse
Summary: The study identified a rare 1:2 CaM:peptide binding mode in the CaM-CK complex, demonstrating that each CaM domain can independently bind CK peptide in a Ca2+-dependent manner. While the overall binding mode is similar between muscle or brain-type CK peptides, the opposite binding orientation of the N-terminal domain peptides may lead to distinct binding modes and regulation of full-length CK isoforms.
CURRENT RESEARCH IN STRUCTURAL BIOLOGY
(2021)
Article
Chemistry, Multidisciplinary
Nandan Haloi, Archit Kumar Vasan, Emily J. Geddes, Arjun Prasanna, Po-Chao Wen, William W. Metcalf, Paul J. Hergenrother, Emad Tajkhorshid
Summary: The introduction of a primary amine can enhance the permeability of bacterial outer membranes in certain contexts, as shown through molecular dynamics simulations and free energy calculations. The amine facilitates antibiotic permeation by aligning the antibiotic molecule's dipole with the protein channel's electric field and forming favorable electrostatic interactions with specific residues. This study provides insights into the importance of primary amines in antibiotic permeation and offers a new computational approach for calculating free energy in processes where relevant molecular conformations cannot be efficiently captured.