Article
Engineering, Biomedical
Jefferson O. Abaricia, Arth H. Shah, Rene Olivares-Navarrete
Summary: Recent studies have shown that neutrophils regulate NET formation in response to physical and mechanical cues from biomaterials through integrin/FAK signaling pathways. Neutrophils on higher stiffness substrates exhibit increased NET formation and pro-inflammatory cytokine secretion, with fibronectin being the most potent inducer of NET formation in a stiffness-dependent manner. Inhibition of FAK activity abolishes the stiffness-dependent increase in NET formation and pro-inflammatory molecule secretion.
Article
Chemistry, Multidisciplinary
Chunlei Zhang, Yuan Wang, Zifeng Zhen, Jiayi Li, Jing Su, Congying Wu
Summary: Cells respond to both biochemical and biomechanical changes in their microenvironment, and this study reveals an integrin-GSK3 beta-FTO-mTOR axis that can sense substrate stiffness and promote cell growth on rigid substrates while also providing resistance to cell death upon matrix detachment. The study demonstrates that substrate stiffening activates mTORC1 and increases mTOR levels through integrins and GSK3 beta-FTO mediated mRNA m6A modification, promoting anabolic metabolism. Inhibition of this axis enhances autophagy upon ECM detachment, providing tumor cells resilience against anoikis. These findings highlight the importance of mechanical force in cellular metabolism and its role in tumor growth and metastasis.
Review
Oncology
Mehak Passi, Stefan Zahler
Summary: Hepatocellular carcinoma (HCC) is a major cause of cancer-related deaths worldwide, with most cases being associated with chronic liver fibrosis which leads to increased liver tissue stiffness. Changes in tissue stiffness affect mechanical signaling pathways, modulating the progression of HCC-related genes. However, mechanical signaling pathways are still less emphasized in comparison to classical biochemical signaling pathways in our understanding of cancer.
Review
Endocrinology & Metabolism
Nicole R. Gould, Olivia M. Torre, Jenna M. Leser, Joseph P. Stains
Summary: Bone is a mechano-responsive tissue that adapts to changes in its mechanical environment. Mechanical stress is crucial for bone mass and quality regulation, and understanding how bone cells sense and transduce these mechanical cues is important. While individual cytoskeletal components have been identified as mechano-sensors in bone, the interconnectedness and collaboration of the entire cytoskeleton may be essential for proper bone cell mechano-transduction.
Review
Cell Biology
Caroline Wilde, Jakob Mitgau, Tomas Suchy, Torsten Schoeneberg, Ines Liebscher
Summary: Incorporating mechanical cues into cellular responses allows cells to perceive and respond to physical properties such as vibration and pressure. Mechanical forces shape cellular responses and tissue development. GPCRs, including angiotensin II type 1 receptor and adrenergic, apelin, histamine, parathyroid hormone 1, and orphan receptors, play a crucial role in mechanosensation. Different types of mechanical activation, such as shear stress and cell swelling/stretch, affect these receptors. The contribution of force-from-lipid and force-from-tether models in ion channels is also discussed.
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
(2022)
Article
Neurosciences
Bryce W. Duncan, Vishwa Mohan, Sarah D. Wade, Young Truong, Alexander Kampov-Polevoi, Brenda R. Temple, Patricia F. Maness
Summary: Research has revealed that Semaphorin 3F, through its holoreceptor complex, plays a role in developmental pruning of dendritic spines, activating different proteins through two signaling pathways to facilitate spine remodeling. This expands our understanding of critical events in shaping neuronal networks and may shed light on spine dysgenesis in diseases such as autism, bipolar disorder, and schizophrenia.
MOLECULAR NEUROBIOLOGY
(2021)
Article
Cell Biology
Lisann Esser, Ronald Springer, Georg Dreissen, Lukas Loevenich, Jens Konrad, Nico Hampe, Rudolf Merkel, Bernd Hoffmann, Erik Noetzel
Summary: Cell contractility regulates epithelial tissue geometry development and homeostasis. We developed an elastomeric pillar cage (EPC) array to quantify cell contractility as a mechanoresponse of epithelial microtissues to substrate stiffness and topography. This work introduced a versatile biophysical tool to explore mechanobiological regulation circuits driving low and high-tensional states during microtissue development and homeostasis.
Review
Biochemistry & Molecular Biology
Shiela C. C. Samson, Akib M. M. Khan, Michelle C. C. Mendoza
Summary: The RAS-ERK pathway is crucial in promoting cell migration and invasion, with steady-state ERK activity playing a role in promoting both single cell and collective migration and invasion. ERK drives actin polymerization and adhesion turnover for edge protrusion, while cell contraction stimulates cell movement in epithelial sheets.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2022)
Article
Engineering, Biomedical
Peizheng Wu, Kazuya Yanagi, Kazuki Yokota, Masataka Hakamada, Mamoru Mabuchi
Summary: The surface topology of substrates strongly affects cell behaviors, and the correlation between topological spacing and cell responses is still debated. Nanoporous gold substrate affects cell adhesion, but not osteogenic or adipogenic differentiation. The unusual effects may be related to the multi-branching of focal adhesion.
JOURNAL OF MATERIALS SCIENCE-MATERIALS IN MEDICINE
(2023)
Article
Cell Biology
Manos Mavrakis, M. Angeles Juanes
Summary: Cell movement is influenced by the turnover of focal adhesions, which traditionally was believed to be triggered by microtubules. However, recent research has discovered other molecular players that affect actin cytoskeleton dynamics, enabling directed cell migration.
CURRENT OPINION IN CELL BIOLOGY
(2023)
Article
Microbiology
Courtney M. Klappenbach, Nicholas M. Negretti, Jesse Aaron, Teng-Leong Chew, Michael E. Konkel
Summary: Our study reveals that C. jejuni infection alters the size and topology of focal adhesions in epithelial cells, leading to changes in cell adhesion strength and motility. The increased phosphorylation of paxillin and altered turnover at focal adhesions may contribute to the effects on cell behavior. Additionally, inhibiting protein synthesis or using specific mutants of C. jejuni can partially reverse these effects, suggesting a potential mechanism for the observed restricted intestinal repair in infected animals.
Article
Multidisciplinary Sciences
Nydia Tejeda-Munoz, Marco Morselli, Yuki Moriyama, Pooja Sheladiya, Matteo Pellegrini, Edward M. De Robertis
Summary: During canonical Wnt signaling, Wnt induces the endocytosis of focal adhesion proteins and depletion of Integrin beta 1 from the cell surface. This endocytosis leads to changes in the cytoskeleton and is accompanied by the sequestration of Integrin beta 1 within membrane-bounded organelles containing glycogen syntase kinase 3 and focal adhesion-associated proteins.
Article
Cell Biology
Lidia Gaffke, Estera Rintz, Karolina Pierzynowska, Grzegorz Wegrzyn
Summary: The main approach in current therapy for mucopolysaccharidosis (MPS) is to reduce glycosaminoglycan (GAG) levels in cells, which are considered the main cause of the disease. This study aimed to evaluate changes in the actin cytoskeleton and focal adhesion in cells from MPS patients and MPS I mouse model, and determine if they could be potential therapeutic targets for different MPS types. Western-blotting, flow cytometry, and transcriptomic analyses were used. Significant changes in the expression of genes involved in the actin cytoskeleton structure/functions were identified, suggesting the actin cytoskeleton as a potential therapeutic target for MPS.
Review
Pharmacology & Pharmacy
Sheng Chen, Tailin He, Yiming Zhong, Mingjue Chen, Qing Yao, Di Chen, Zengwu Shao, Guozhi Xiao
Summary: The skeletal system plays crucial roles in body shaping, support and movement, protection of internal organs, production of blood cells, and regulation of calcium and phosphate metabolism. Skeletal diseases and disorders such as osteoporosis, arthritis, and intervertebral disc degeneration are becoming increasingly common and have significant social and economic impacts. This review focuses on the molecular mechanisms and therapeutic targets of focal adhesion proteins in skeletal diseases.
ACTA PHARMACEUTICA SINICA B
(2023)
Article
Chemistry, Multidisciplinary
Pasquale Sacco, Francesco Piazza, Chiara Pizzolitto, Gabriele Baj, Francesco Brun, Eleonora Marsich, Ivan Donati
Summary: This study presents a strategy to control the dissipation rate of viscoplastic substrates while precisely regulating linear elasticity, and reveals the crucial link between this material property and cellular responses in 2D cultures.
ADVANCED FUNCTIONAL MATERIALS
(2022)