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Cells
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Mechanotransduction in Cell Functioning and (Patho)physiology
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Mechanotransduction in Cell Functioning and (Patho)physiology

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cell Motility and Adhesion".

Deadline for manuscript submissions: closed (15 March 2024) | Viewed by 10574

Special Issue Editors

Dr. Carsten Schulte

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Guest Editor
Department of Biomedical and Clinical Sciences (DIBIC) "L. Sacco", LITA Vialba Campus, Università degli Studi di Milano, Via Gian Battista Grassi, 74-20157 Milano, Italy
Interests: mechanotransduction; cellular mechanobiology; integrins; cell adhesion; cell migration; cell invasion; metastasis; biomaterials; cell-microenvironment interactions; cytoskeleton; cell differentiation
Special Issues, Collections and Topics in MDPI journals
Dr. Carla Perego

E-Mail Website
Guest Editor
Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Milan, Italy
Interests: adhesion molecules; cellular mechanobiology; mitochondrial dynamics; vesicular trafficking; islet of Langerhans; beta cells differentiation; diabetes mellitus; pancreatic tumors; glia–neuron interactions
Special Issues, Collections and Topics in MDPI journals
Dr. Carmelo Ferrai

E-Mail Website
Guest Editor
Institute of Pathology, University Medical Center Göttingen, Robert-Koch-Str. 40, 37075 Göttingen, Germany
Interests: cell response to nanotopography; RNAPII & transcription regulation; chromatin conformation & nuclear architecture; pluripotency; cell plasticity
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Years of intense research established nowadays the general concept that mechanotransduction, i.e., the signalling pathway by which cells sense and interpret microenvironmental physical forces (e.g., tension, compression, distortion, friction) and biophysical cues (e.g., rigidity, topography), affects virtually all cell biological processes, and therefore tissue homeostasis and organ development. The mechanotransductive sequence is characterised by an intricate force-based dialogue and interplay between the involved components, such as the extracellular matrix, the glycocalyx, the cell membrane with its embedded surface receptors (in particular integrin adhesion complexes), the cytoskeleton, the nuclear envelope, and chromatin. This very complexity of the pathway still leaves many questions open. This is even more so the case with respect to the aberrations in mechanotransductive processes and structures that have been associated with many pathophysiological situations, such as cancers, metastases, neurodegenerative and cardiovascular diseases. However, the recent emergence of mechanotherapeutics, i.e., drugs that target specifically mechanotransductive key players or structures, highlights the potential of looking at mechanotransduction also from a biomedical perspective, encouraged by first promising results in clinical trials.

We are pleased to invite you to contribute to this Special Issue “Mechanotransduction in cell functioning and (patho)physiology”. This SI aims to dissect basic research on fundamental mechanisms of mechanotransductive processes, as well as development of novel mechanobiological approaches, or preclinical studies related to mechanotransduction. We would be glad to receive original research articles, as well as reviews, that may include (but are certainly not limited to) the following topics: 

  • Cell biological studies in response to mechanotransductive stimuli (in bulk or single cell analyses)
  • Extracellular matrix or glycocalyx effects on mechanotransduction
  • Forces in mechanotransduction
  • Tissue level studies related to mechanobiology
  • Mechanobiology and metabolism
  • Mechanobiology in chromatin remodelling and epigenetic regulation
  • Pathophysiological aberrations associated with mechanotransductive components or structures
  • Mechanopharmacology
  • Bioinformatic tools integrating proteomic-genomic data and computational modelling applied to mechanotransduction. 

Dr. Carsten Schulte
Dr. Carla Perego
Dr. Carmelo Ferrai
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cells is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • mechanotransduction
  • extracellular matrix
  • glycocalyx
  • integrins
  • cytoskeleton
  • regenerative medicine
  • mechanotherapeutics
  • biomaterials
  • tissue engineering
  • mechanobiology
  • biophysics
  • cell identity
  • epigenetic regulation.

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Related Special Issue

Published Papers (4 papers)

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Research

24 pages, 6285 KiB  
Article
Tight Regulation of Mechanotransducer Proteins Distinguishes the Response of Adult Multipotent Mesenchymal Cells on PBCE-Derivative Polymer Films with Different Hydrophilicity and Stiffness
by Chiara Argentati, Francesco Morena, Giulia Guidotti, Michelina Soccio, Nadia Lotti and Sabata Martino
Cells 2023, 12(13), 1746; https://doi.org/10.3390/cells12131746 - 29 Jun 2023
Cited by 2 | Viewed by 1437
Abstract
Mechanotransduction is a molecular process by which cells translate physical stimuli exerted by the external environment into biochemical pathways to orchestrate the cellular shape and function. Even with the advancements in the field, the molecular events leading to the signal cascade are still [...] Read more.
Mechanotransduction is a molecular process by which cells translate physical stimuli exerted by the external environment into biochemical pathways to orchestrate the cellular shape and function. Even with the advancements in the field, the molecular events leading to the signal cascade are still unclear. The current biotechnology of tissue engineering offers the opportunity to study in vitro the effect of the physical stimuli exerted by biomaterial on stem cells and the mechanotransduction pathway involved in the process. Here, we cultured multipotent human mesenchymal/stromal cells (hMSCs) isolated from bone marrow (hBM-MSCs) and adipose tissue (hASCs) on films of poly(butylene 1,4-cyclohexane dicarboxylate) (PBCE) and a PBCE-based copolymer containing 50 mol% of butylene diglycolate co-units (BDG50), to intentionally tune the surface hydrophilicity and the stiffness (PBCE = 560 Mpa; BDG50 = 94 MPa). We demonstrated the activated distinctive mechanotransduction pathways, resulting in the acquisition of an elongated shape in hBM-MSCs on the BDG50 film and in maintaining the canonical morphology on the PBCE film. Notably, hASCs acquired a new, elongated morphology on both the PBCE and BDG50 films. We found that these events were mainly due to the differences in the expression of Cofilin1, Vimentin, Filamin A, and Talin, which established highly sensitive machinery by which, rather than hASCs, hBM-MSCs distinguished PBCE from BDG50 films. Full article
(This article belongs to the Special Issue Mechanotransduction in Cell Functioning and (Patho)physiology)
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21 pages, 4509 KiB  
Article
Oxygen-Glucose Deprivation in Organotypic Hippocampal Cultures Leads to Cytoskeleton Rearrangement and Immune Activation: Link to the Potential Pathomechanism of Ischaemic Stroke
by Natalia Bryniarska-Kubiak, Andrzej Kubiak, Ewa Trojan, Julita Wesołowska, Małgorzata Lekka and Agnieszka Basta-Kaim
Cells 2023, 12(11), 1465; https://doi.org/10.3390/cells12111465 - 24 May 2023
Cited by 2 | Viewed by 2500
Abstract
Ischaemic stroke is characterized by a sudden loss of blood circulation to an area of the brain, resulting in a corresponding loss of neurologic function. As a result of this process, neurons in the ischaemic core are deprived of oxygen and trophic substances [...] Read more.
Ischaemic stroke is characterized by a sudden loss of blood circulation to an area of the brain, resulting in a corresponding loss of neurologic function. As a result of this process, neurons in the ischaemic core are deprived of oxygen and trophic substances and are consequently destroyed. Tissue damage in brain ischaemia results from a complex pathophysiological cascade comprising various distinct pathological events. Ischaemia leads to brain damage by stimulating many processes, such as excitotoxicity, oxidative stress, inflammation, acidotoxicity, and apoptosis. Nevertheless, less attention has been given to biophysical factors, including the organization of the cytoskeleton and the mechanical properties of cells. Therefore, in the present study, we sought to evaluate whether the oxygen-glucose deprivation (OGD) procedure, which is a commonly accepted experimental model of ischaemia, could affect cytoskeleton organization and the paracrine immune response. The abovementioned aspects were examined ex vivo in organotypic hippocampal cultures (OHCs) subjected to the OGD procedure. We measured cell death/viability, nitric oxide (NO) release, and hypoxia-inducible factor 1α (HIF-1α) levels. Next, the impact of the OGD procedure on cytoskeletal organization was evaluated using combined confocal fluorescence microscopy (CFM) and atomic force microscopy (AFM). Concurrently, to find whether there is a correlation between biophysical properties and the immune response, we examined the impact of OGD on the levels of crucial ischaemia cytokines (IL-1β, IL-6, IL-18, TNF-α, IL-10, IL-4) and chemokines (CCL3, CCL5, CXCL10) in OHCs and calculated Pearsons’ and Spearman’s rank correlation coefficients. The results of the current study demonstrated that the OGD procedure intensified cell death and nitric oxide release and led to the potentiation of HIF-1α release in OHCs. Moreover, we presented significant disturbances in the organization of the cytoskeleton (actin fibers, microtubular network) and cytoskeleton-associated protein 2 (MAP-2), which is a neuronal marker. Simultaneously, our study provided new evidence that the OGD procedure leads to the stiffening of OHCs and a malfunction in immune homeostasis. A negative linear correlation between tissue stiffness and branched IBA1 positive cells after the OGD procedure suggests the pro-inflammatory polarization of microglia. Moreover, the negative correlation of pro- and positive anti-inflammatory factors with actin fibers density indicates an opposing effect of the immune mediators on the rearrangement of cytoskeleton induced by OGD procedure in OHCs. Our study constitutes a basis for further research and provides a rationale for integrating biomechanical and biochemical methods in studying the pathomechanism of stroke-related brain damage. Furthermore, presented data pointed out the interesting direction of proof-of-concept studies, in which follow-up may establish new targets for brain ischemia therapy. Full article
(This article belongs to the Special Issue Mechanotransduction in Cell Functioning and (Patho)physiology)
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22 pages, 5707 KiB  
Article
The LINC Complex Inhibits Excessive Chromatin Repression
by Daria Amiad Pavlov, CP Unnikannan, Dana Lorber, Gaurav Bajpai, Tsviya Olender, Elizabeth Stoops, Adriana Reuveny, Samuel Safran and Talila Volk
Cells 2023, 12(6), 932; https://doi.org/10.3390/cells12060932 - 18 Mar 2023
Cited by 6 | Viewed by 2883
Abstract
The Linker of Nucleoskeleton and Cytoskeleton (LINC) complex transduces nuclear mechanical inputs suggested to control chromatin organization and gene expression; however, the underlying mechanism is currently unclear. We show here that the LINC complex is needed to minimize chromatin repression in muscle tissue, [...] Read more.
The Linker of Nucleoskeleton and Cytoskeleton (LINC) complex transduces nuclear mechanical inputs suggested to control chromatin organization and gene expression; however, the underlying mechanism is currently unclear. We show here that the LINC complex is needed to minimize chromatin repression in muscle tissue, where the nuclei are exposed to significant mechanical inputs during muscle contraction. To this end, the genomic binding profiles of Polycomb, Heterochromatin Protein1 (HP1a) repressors, and of RNA-Pol II were studied in Drosophila larval muscles lacking functional LINC complex. A significant increase in the binding of Polycomb and parallel reduction of RNA-Pol-II binding to a set of muscle genes was observed. Consistently, enhanced tri-methylated H3K9 and H3K27 repressive modifications and reduced chromatin activation by H3K9 acetylation were found. Furthermore, larger tri-methylated H3K27me3 repressive clusters, and chromatin redistribution from the nuclear periphery towards nuclear center, were detected in live LINC mutant larval muscles. Computer simulation indicated that the observed dissociation of the chromatin from the nuclear envelope promotes growth of tri-methylated H3K27 repressive clusters. Thus, we suggest that by promoting chromatin–nuclear envelope binding, the LINC complex restricts the size of repressive H3K27 tri-methylated clusters, thereby limiting the binding of Polycomb transcription repressor, directing robust transcription in muscle fibers. Full article
(This article belongs to the Special Issue Mechanotransduction in Cell Functioning and (Patho)physiology)
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20 pages, 5719 KiB  
Article
Nanotopography and Microconfinement Impact on Primary Hippocampal Astrocyte Morphology, Cytoskeleton and Spontaneous Calcium Wave Signalling
by Anita Previdi, Francesca Borghi, Filippo Profumo, Carsten Schulte, Claudio Piazzoni, Jacopo Lamanna, Gabriella Racchetti, Antonio Malgaroli and Paolo Milani
Cells 2023, 12(2), 293; https://doi.org/10.3390/cells12020293 - 12 Jan 2023
Cited by 5 | Viewed by 2243
Abstract
Astrocytes’ organisation affects the functioning and the fine morphology of the brain, both in physiological and pathological contexts. Although many aspects of their role have been characterised, their complex functions remain, to a certain extent, unclear with respect to their contribution to brain [...] Read more.
Astrocytes’ organisation affects the functioning and the fine morphology of the brain, both in physiological and pathological contexts. Although many aspects of their role have been characterised, their complex functions remain, to a certain extent, unclear with respect to their contribution to brain cell communication. Here, we studied the effects of nanotopography and microconfinement on primary hippocampal rat astrocytes. For this purpose, we fabricated nanostructured zirconia surfaces as homogenous substrates and as micrometric patterns, the latter produced by a combination of an additive nanofabrication and micropatterning technique. These engineered substrates reproduce both nanotopographical features and microscale geometries that astrocytes encounter in their natural environment, such as basement membrane topography, as well as blood vessels and axonal fibre topology. The impact of restrictive adhesion manifests in the modulation of several cellular properties of single cells (morphological and actin cytoskeletal changes) and the network organisation and functioning. Calcium wave signalling was observed only in astrocytes grown in confined geometries, with an activity enhancement in cells forming elongated agglomerates with dimensions typical of blood vessels or axon fibres. Our results suggest that calcium oscillation and wave propagation are closely related to astrocytic morphology and actin cytoskeleton organisation. Full article
(This article belongs to the Special Issue Mechanotransduction in Cell Functioning and (Patho)physiology)
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