Article
Immunology
Chirag Sachar, Lance C. Kam
Summary: This study introduces a method to change the structural rigidity of microscale elastomer pillars using magnetic fields, showing that an increase in pillar spring constant alters the morphology of T cells and IL-2 secretion. This approach separates local substrate stiffness from long-range structural rigidity, revealing new insights into T cell interaction with their environment.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Multidisciplinary Sciences
Rocio G. Sampayo, Mason Sakamoto, Madeline Wang, Sanjay Kumar, David V. Schaffer
Summary: During the process of cell differentiation into tissues, cells are influenced by mechanical signals from the extracellular matrix (ECM), which regulate their fate. The activation of Rho GTPases plays a key role in sensing these cues, but the regulation and integration of the activation dynamics is still unclear. This study found that ECM stiffness cues not only alter the magnitude but also the temporal frequency of RhoA and Cdc42 activation in adult neural stem cells (NSCs). Further experiments using optogenetics showed that the frequency of RhoA and Cdc42 activation drives astrocytic versus neuronal differentiation, highlighting the functional significance of these dynamics.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Review
Biochemistry & Molecular Biology
Chieh-Ren Hsia, Daniel P. Melters, Yamini Dalal
Summary: All life forms have the ability to sense and respond to mechanical stimuli through mechanotransduction pathways, leading to fast and sustained mechanoresponses. Mechanoresponses are stored as epigenetic modifications, including chromatin structure alterations. The mechanisms by which mechanotransduction alters chromatin structure and its effects on the cellular environment are still unclear.
JOURNAL OF MOLECULAR BIOLOGY
(2023)
Article
Chemistry, Multidisciplinary
Alexander S. Zhovmer, Alexis Manning, Chynna Smith, James B. Hayes, Dylan T. Burnette, Jian Wang, Alexander X. Cartagena-Rivera, Nikolay V. Dokholyan, Rakesh K. Singh, Erdem D. Tabdanov
Summary: The study demonstrates an antagonistic mechanical balance within the dynein-kinesin microtubular motor system, where dynein activity drives inward compaction of the microtubular network, while kinesins bundle and expand MTs into giant circular bands. This balance controls the 3D architecture, mechanics, and cell-microenvironment interactions of cells through orthogonal mechanisms of MT network reorganization.
Article
Multidisciplinary Sciences
Jana Slovakova, Mateusz Sikora, Feyza Nur Arslan, Silvia Caballero-Mancebo, S. F. Gabriel Krens, Walter A. Kaufmann, Jack Merrin, Carl-Philipp Heisenberg
Summary: The tension of the actomyosin cell cortex is crucial in determining the growth and size of cell-cell contact. This relationship increases proportionally within a certain range of tension, but inversely scales above a critical threshold. This switch is caused by cortical tension promoting the anchoring of E-cadherin to the actomyosin cytoskeleton, thereby increasing clustering and stability of E-cadherin at the contact.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Cell Biology
Priti Agarwal, Ronen Zaidel-Bar
Summary: Mechanical forces generated by living cells play a crucial role in embryogenesis by directly influencing cell movement and activating mechanosensitive signaling. These forces are involved in cell fate determination, growth, morphogenesis, and organogenesis, demonstrating their importance in shaping the development of organisms across different species.
CURRENT OPINION IN CELL BIOLOGY
(2021)
Article
Chemistry, Multidisciplinary
Pingping Han, Cedryck Vaquette, Abdalla Abdal-hay, Saso Ivanovski
Summary: The study evaluated human primary osteoblast cells' sensing and response to random and aligned PCL fibrous scaffolds, revealing that aligned fibers can result in elongated cell and nucleus shape, as well as increased global DNA methylation levels, which have long-term effects on osteoblast osteogenic differentiation.
Article
Materials Science, Biomaterials
Carolin Grandy, Fabian Port, Jonas Pfeil, Mariana Azevedo Gonzalez Oliva, Massimo Vassalli, Kay-Eberhard Gottschalk
Summary: Cells are connected to the extracellular matrix through the focal adhesion complex, which also acts as a force sensor. However, the effect of tension on the structure of focal adhesions is still poorly understood. In this study, the location of key focal adhesion proteins, including vinculin, paxillin, and actin, was analyzed under tension using micropatterning and metal-induced energy transfer measurements. The results show that actin is particularly affected by the force balance, and blocking mechanosensitive ion channels significantly alters the architecture of focal adhesions and the distribution of these proteins.
BIOMATERIALS ADVANCES
(2023)
Article
Engineering, Mechanical
Michael Sheetz
Summary: The field of Mechanobiology is still in its early stages, where the molecular processes used by cells to mechanically create organism forms are being uncovered. One known mechanosensing process involves the sensing of matrix rigidity, where cell rigidity sensors play a crucial role in inhibiting unwanted adult cell growth on soft surfaces. Interestingly, transformed cells are found to be mechanically sensitive and can be targeted with mechanical therapies to inhibit cancer growth.
EXTREME MECHANICS LETTERS
(2021)
Review
Cell Biology
Alberto Elosegui-Artola
Summary: The mechanical properties of the extracellular matrix play a crucial role in regulating cell and tissue behavior. While much research has focused on the elasticity of the extracellular matrix, the influence of its viscosity on cell behavior remains relatively understudied. Recent findings have highlighted the importance of the extracellular matrix's viscoelasticity in cell and tissue dynamics.
CURRENT OPINION IN CELL BIOLOGY
(2021)
Article
Chemistry, Multidisciplinary
Soham Ghosh, Victor Crespo Cuevas, Benjamin Seelbinder, Corey P. Neu
Summary: The study introduces nuclear elastography technology to quantify the relative elasticity of heterochromatin and euchromatin domains within the cell nucleus; experiments reveal rapid changes in relative elasticity between these two regions during cellular deformation; disruption of specific nuclear membrane proteins affects intranuclear elasticity distribution, leading to similarities between heterochromatin and euchromatin.
Article
Engineering, Biomedical
E. Benvenuti, G. A. Reho, S. Palumbo, M. Fraldi
Summary: We demonstrate that the contractile activity of a cell interacting with the substrate can be captured by a non-linear elastic mechanical system, consisting of a tensile element and a buckling-prone component, exchanging forces with the surroundings through an extracellular matrix-focal adhesion complex. The mechanical sensitivity of the focal adhesion plaque is triggered by pre-strain-driven buckling, induced by pre-contraction or pre-polymerization.
JOURNAL OF THE MECHANICAL BEHAVIOR OF BIOMEDICAL MATERIALS
(2022)
Article
Multidisciplinary Sciences
Amir Vahabikashi, Suganya Sivagurunathan, Fiona Ann Sadsad Nicdao, Yu Long Han, Chan Young Park, Mark Kittisopikul, Xianrong Wong, Joseph R. Tran, Gregg G. Gundersen, Karen L. Reddy, G. W. Gant Luxton, Ming Guo, Jeffrey J. Fredberg, Yixian Zheng, Stephen A. Adam, Robert D. Goldman
Summary: The interactions between the nucleus and cytoskeleton play a crucial role in regulating cellular mechanics. A-type lamins engage with F-actin and vimentin intermediate filaments to modulate cortical stiffness and contractility, while B-type lamins predominantly interact with vimentin intermediate filaments to regulate cytoplasmic stiffness and contractility. The loss of each lamin isoform affects nucleocytoskeletal interactions and cellular mechanics.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Chemistry, Multidisciplinary
Valentin Romanov, Giulia Silvani, Huiyu Zhu, Charles D. Cox, Boris Martinac
Summary: This study demonstrates the high-throughput characterization of adherent cells using acoustic force spectroscopy (AFS), showing that cells' stiffness and viscoelasticity can be influenced by temperature and pharmacological treatments targeting the membrane-cytoskeleton interface. Furthermore, the ability to differentiate between cells based on protein expression levels was shown by rapidly probing over 1000 cells from three different cell lines expressing different levels of the mechanosensitive protein Piezo1 using AFS.
Article
Materials Science, Biomaterials
Allison N. Ramey-Ward, Yixiao Dong, Jin Yang, Hiroaki Ogasawara, Elizabeth C. Bremer-Sai, Olga Brazhkina, Christian Franck, Michael Davis, Khalid Salaita
Summary: In this study, hydrogels were transformed into mechanically active substrates by doping optomechanical actuator (OMA) nanoparticles. The response could be controlled by NIR intensity and OMA density within the gel and is applicable to other hydrogel materials. The mechanical stimulation of hydrogels enhanced myogenesis and rescued differentiation in a chronic inflammation model. The findings establish OMA-actuated biomaterials as a powerful tool for in vitro mechanical manipulation with broad applications in the field of mechanobiology.
ACS BIOMATERIALS SCIENCE & ENGINEERING
(2023)
News Item
Physics, Multidisciplinary
M. -A. Fardin, B. Ladoux
Summary: A class of biological matter, including elongated cells and filaments, can be described in the context of active nematic liquid crystals. Within these systems, topological defects emerge and lead to remarkable collective behaviors.
Article
Biophysics
Julia Eckert, Jack J. W. A. van Loon, Lukas M. Eng, Thomas Schmidt
Summary: Studies show that microgravity and hypergravity impact cell shape, elasticity, and motility, with changes in cell traction forces under hypergravity conditions possibly linked to cytoskeleton reorganization and reinforcement.
BIOPHYSICAL JOURNAL
(2021)
Review
Biophysics
Feyza Nur Arslan, Julia Eckert, Thomas Schmidt, Carl-Philipp Heisenberg
Summary: This review article focuses on the importance and research status of cell-cell adhesion, including descriptions and regulations at different levels, as well as discussions on the molecular and cellular mechanisms of cell-cell adhesion.
BIOPHYSICAL JOURNAL
(2021)
Article
Cell Biology
Radoslaw J. Gora, Babette de Jong, Patrick van Hage, Mary Ann Rhiemus, Fjodor van Steenis, John van Noort, Thomas Schmidt, Marcel J. M. Schaaf
Summary: In this study, single-molecule microscopy was used to investigate the dynamics of H-Ras protein in zebrafish embryos. The results showed the presence of fast- and slow-diffusing subpopulations of molecules within the plasma membrane, which are influenced by the structure and composition of the membrane. Additionally, differences between cells within the same embryo were found to contribute to the variability in the data. These findings highlight the importance of single-molecule microscopy for studying factors influencing protein dynamics in an intact living organism.
DISEASE MODELS & MECHANISMS
(2022)
Review
Biochemistry & Molecular Biology
Min-Hyeok Kim, Danny van Noort, Jong Hwan Sung, Sungsu Park
Summary: Extracellular vesicles (EVs) play important roles in the gut-brain axis (GBA), yet their roles in the gut microenvironment are less highlighted. Advances in organ-on-a-chip (OOC) technologies offer a promising solution for current challenges in GBA research.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
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
Biochemical Research Methods
Rick Rodrigues de Mercado, Hedde VAN Hoorn, Martin DE Valois, Claude Backendorf, Julia Eckert, Thomas Schmidt
Summary: High-resolution and super-resolution techniques are commonly used in imaging life cells and tissue, but sample inhomogeneities and resulting astigmatism can affect the accuracy of observations. A simple model and a figure-of-merit are introduced to assess the importance of astigmatism in an experiment. Astigmatism caused by the cell's nucleus can result in significant aberrations beyond the accuracy of super-resolution techniques, while astigmatism generated by small objects may not be significant in typical super-resolution experimentation.
BIOMEDICAL OPTICS EXPRESS
(2022)
Article
Oncology
Stacey E. P. Joosten, Marius Wellenstein, Rutger Koornstra, Annelot van Rossum, Joyce Sanders, Vincent van der Noort, Maria C. Ferrandez, Rolf Harkes, Ingrid A. M. Mandjes, Hilde Rosing, Alwin Huitema, Jos H. Beijnen, Jelle Wesseling, Paul J. van Diest, Hugo M. Horlings, Sabine C. Linn, Wilbert Zwart
Summary: Window studies focusing on molecular changes in short timeframes are gaining attention. Decreased Ki67 levels in tumor cells are often used as an indicator of treatment response. The study compared pre- and postmenopausal breast cancer patients in a trial focused on endocrine therapy, finding that the decrease in Ki67 levels was smaller in premenopausal women and was directly related to post-treatment estradiol levels. These findings suggest that IHC-based Ki67 may be a suitable biomarker for evaluating tamoxifen response in premenopausal breast cancer patients, with the anti-proliferative effect size depending on estradiol levels.
Article
Oncology
I Nederlof, S. Hajizadeh, F. Sobhani, S. E. A. Raza, K. AbdulJabbar, R. Harkes, M. J. van de Vijver, R. Salgado, C. Desmedt, M. Kok, Y. Yuan, H. M. Horlings
Summary: This study evaluated the spatial patterns of tumor infiltrating lymphocytes (TILs) and fibroblasts in ER(+)HER2(-) breast cancer and found their association with prognosis and immune-related molecular characteristics.
Article
Physics, Multidisciplinary
Surabhi Sonam, Lakshmi Balasubramaniam, Shao-Zhen Lin, Ying Ming Yow Ivan, Irina Pi-Jauma, Cecile Jebane, Marc Karnat, Yusuke Toyama, Philippe Marcq, Jacques Prost, Rene-Marc Mege, Jean-Francois Rupprecht, Benoit Ladoux
Summary: Epithelial cells are influenced by mechanical stress and abrasion, impacting their integrity. Culturing epithelial cells on two-dimensional hydrogels showed that soft substrates resulted in a loss of epithelial monolayer integrity through hole formation. This rupture was associated with cellular stretching and cell division events.
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
Multidisciplinary Sciences
Maria Mytiliniou, Joeri A. J. Wondergem, Thomas Schmidt, Doris Heinrich
Summary: Intracellular transport is crucial for cell growth and survival, and malfunction in this process is linked to neurodegenerative diseases. This study investigates the motion of lysosomes in neurites and reveals that the alignment of neurites significantly affects the lysosomal motion.
JOURNAL OF THE ROYAL SOCIETY INTERFACE
(2022)
Article
Chemistry, Physical
Guido L. A. Kusters, Paul van der Schoot, Cornelis Storm
Summary: Recently, three distinct and well-separated transient regimes were discovered in the dynamics of shape-shifting liquid crystal network films when an alternating electric field is switched on. A time-dependent Landau theory was employed to explain the existence of three time scales by coupling local volume generation to the degree of orientational order of mesogens in a viscoelastic network. The study revealed that the three time scales depend significantly on the film thickness, indicating a transition from thin film to bulk. The emergence of spatial inhomogeneities in the bulk of the film, in the form of domains separated by regions of suppressed expansion, was found to cause variations in the film's overall expansion and may lead to uncontrolled patterning. The formation of domains can be suppressed by reducing film thickness, increasing linear dimensions of the mesogens, or enhancing their degree of orientational order.
Article
Physics, Fluids & Plasmas
Guido L. A. Kusters, Nicholas B. Tito, Cornelis Storm, Paul van der Schoot
Summary: Liquid crystal networks combine the responsiveness of liquid crystalline mesogens to electric fields with the (visco)elastic properties of a polymer network. The study shows that the response of liquid crystal networks permeates throughout the film, impacting the timescale of macroscopic deformation. By adjusting the aspect ratio of the mesogens and their degree of orientational order in the polymer network, the permeation rate can be controlled to achieve optimal results for future applications involving molecular cargo transport or release in liquid crystal network films.
