Special Issue "Mechanotransduction in Control of Cell Fate and Function"

A special issue of Cells (ISSN 2073-4409).

Deadline for manuscript submissions: closed (30 November 2019).

Special Issue Editors

Prof. Carla Perego
E-Mail Website
Guest Editor
Lab of Molecular and Cellular Physiology, Dept. of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Via Trentacoste, 2-20134 Milan, Italy
Interests: molecular mechanisms of neurotransmitter and hormone release; signal transduction; membrane protein trafficking; neurotransmitter receptor and transporter; cell–cell and cell–matrix; endocrine cells of the pancreas; neurons; diabetes; Parkinson disease
Dr. Carsten Schulte
E-Mail Website
Guest Editor
Interdisciplinary Centre for Nanostructured Materials and Interfaces (CIMaINa) at the Department of Physics, Università degli Studi di Milano, Via Celoria 16, 20133 Milan, Italy
Interests: mechanotransduction; mechanobiology; integrin signalling; biophysics; cell adhesion; cell migration; neuronal differentiation; cancer cell biology; biomaterials

Special Issue Information

Dear Colleagues,

Mechanotransduction defines the process by which cells perceive and respond to microenvironmental physical forces (e.g., tension, compression, distortion, friction) and cues (e.g., rigidity, topography) by activating a cellular signaling sequence mediated by mechanosensitive cellular components and gene expression. Although the underlying molecular mechanisms have not been completely understood, increasing evidence suggests that mechanotransduction is critically involved in the control of cell differentiation, tissue homeostasis, and organ development.

This Special Issue welcomes original research and review papers addressing the contribution of biophysical forces and cues deriving from the extracellular microenvironment in shaping stem cell fate. Interdisciplinary applications will stimulate future research in this exciting and rapidly-progressing field.

Prof. Carla Perego
Dr. Carsten Schulte
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 papers will be 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 monthly 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 2000 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
  • stem cells
  • regenerative medicine
  • extracellular matrix
  • biomaterials
  • tissue engineering

Published Papers (6 papers)

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Research

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Open AccessArticle
Copresentation of BMP-6 and RGD Ligands Enhances Cell Adhesion and BMP-Mediated Signaling
Cells 2019, 8(12), 1646; https://doi.org/10.3390/cells8121646 - 15 Dec 2019
Cited by 1
Abstract
We report on the covalent immobilization of bone morphogenetic protein 6 (BMP-6) and its co-presentation with integrin ligands on a nanopatterned platform to study cell adhesion and signaling responses which regulate the transdifferentiation of myoblasts into osteogenic cells. To immobilize BMP-6, the heterobifunctional [...] Read more.
We report on the covalent immobilization of bone morphogenetic protein 6 (BMP-6) and its co-presentation with integrin ligands on a nanopatterned platform to study cell adhesion and signaling responses which regulate the transdifferentiation of myoblasts into osteogenic cells. To immobilize BMP-6, the heterobifunctional linker MU-NHS is coupled to amine residues of the growth factor; this prevents its internalization while ensuring that its biological activity is maintained. Additionally, to allow cells to adhere to such platform and study signaling events arising from the contact to the surface, we used click-chemistry to immobilize cyclic-RGD carrying an azido group reacting with PEG-alkyne spacers via copper-catalyzed 1,3-dipolar cycloaddition. We show that the copresentation of BMP-6 and RGD favors focal adhesion formation and promotes Smad 1/5/8 phosphorylation. When presented in low amounts, BMP-6 added to culture media of cells adhering to the RGD ligands is less effective than BMP-6 immobilized on the surfaces in inducing Smad complex activation and in inhibiting myotube formation. Our results suggest that a local control of ligand density and cell signaling is crucial for modulating cell response. Full article
(This article belongs to the Special Issue Mechanotransduction in Control of Cell Fate and Function)
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Review

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Open AccessFeature PaperReview
Shaping Pancreatic β-Cell Differentiation and Functioning: The Influence of Mechanotransduction
Cells 2020, 9(2), 413; https://doi.org/10.3390/cells9020413 - 11 Feb 2020
Abstract
Embryonic and pluripotent stem cells hold great promise in generating β-cells for both replacing medicine and novel therapeutic discoveries in diabetes mellitus. However, their differentiation in vitro is still inefficient, and functional studies reveal that most of these β-like cells still fail to [...] Read more.
Embryonic and pluripotent stem cells hold great promise in generating β-cells for both replacing medicine and novel therapeutic discoveries in diabetes mellitus. However, their differentiation in vitro is still inefficient, and functional studies reveal that most of these β-like cells still fail to fully mirror the adult β-cell physiology. For their proper growth and functioning, β-cells require a very specific environment, the islet niche, which provides a myriad of chemical and physical signals. While the nature and effects of chemical stimuli have been widely characterized, less is known about the mechanical signals. We here review the current status of knowledge of biophysical cues provided by the niche where β-cells normally live and differentiate, and we underline the possible machinery designated for mechanotransduction in β-cells. Although the regulatory mechanisms remain poorly understood, the analysis reveals that β-cells are equipped with all mechanosensors and signaling proteins actively involved in mechanotransduction in other cell types, and they respond to mechanical cues by changing their behavior. By engineering microenvironments mirroring the biophysical niche properties it is possible to elucidate the β-cell mechanotransductive-regulatory mechanisms and to harness them for the promotion of β-cell differentiation capacity in vitro. Full article
(This article belongs to the Special Issue Mechanotransduction in Control of Cell Fate and Function)
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Open AccessReview
Mechanotransduction in T Cell Development, Differentiation and Function
Cells 2020, 9(2), 364; https://doi.org/10.3390/cells9020364 - 05 Feb 2020
Abstract
Cells in the body are actively engaging with their environments that include both biochemical and biophysical aspects. The process by which cells convert mechanical stimuli from their environment to intracellular biochemical signals is known as mechanotransduction. Exemplifying the reliance on mechanotransduction for their [...] Read more.
Cells in the body are actively engaging with their environments that include both biochemical and biophysical aspects. The process by which cells convert mechanical stimuli from their environment to intracellular biochemical signals is known as mechanotransduction. Exemplifying the reliance on mechanotransduction for their development, differentiation and function are T cells, which are central to adaptive immune responses. T cell mechanoimmunology is an emerging field that studies how T cells sense, respond and adapt to the mechanical cues that they encounter throughout their life cycle. Here we review different stages of the T cell’s life cycle where existing studies have shown important effects of mechanical force or matrix stiffness on a T cell as sensed through its surface molecules, including modulating receptor–ligand interactions, inducing protein conformational changes, triggering signal transduction, amplifying antigen discrimination and ensuring directed targeted cell killing. We suggest that including mechanical considerations in the immunological studies of T cells would inform a more holistic understanding of their development, differentiation and function. Full article
(This article belongs to the Special Issue Mechanotransduction in Control of Cell Fate and Function)
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Open AccessReview
Mechanical Forces as Determinants of Disseminated Metastatic Cell Fate
Cells 2020, 9(1), 250; https://doi.org/10.3390/cells9010250 - 19 Jan 2020
Cited by 2
Abstract
Disseminated metastatic cancer cells represent one of the most relevant causes of disease relapse and associated death for cancer patients, and a therapeutic target of the highest priority. Still, our understanding of how disseminated cancer cells survive in the foreign metastatic environment, and [...] Read more.
Disseminated metastatic cancer cells represent one of the most relevant causes of disease relapse and associated death for cancer patients, and a therapeutic target of the highest priority. Still, our understanding of how disseminated cancer cells survive in the foreign metastatic environment, and eventually cause metastatic outgrowth, remains rather limited. In this review we focus on the cell microenvironment as a key regulator of cell behavior at the metastatic site, and especially on the mechanical properties of the extracellular matrix and associated integrin signaling. We discuss available evidence pointing to a pervasive role of extracellular matrix (ECM) mechanical properties in regulating cancer cell proliferation and survival after dissemination, and propose that this might represent an important bottleneck for cells invading and establishing into a novel tissue. We point to the known molecular players, how these might contribute to modulate the mechanical properties of the metastatic environment, and the response of cells to these cues. Finally, we propose that emerging knowledge on the physical interaction of disseminated metastatic cells and on the downstream mechanotransduction pathways, including YAP/TAZ (Yes-associated protein-1 and WW-domain transcription activator 1) and MRTFs (Myocardin-related transcription factors), may help to identify novel approaches for therapy. Full article
(This article belongs to the Special Issue Mechanotransduction in Control of Cell Fate and Function)
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Open AccessFeature PaperReview
Dysfunctional Mechanotransduction through the YAP/TAZ/Hippo Pathway as a Feature of Chronic Disease
Cells 2020, 9(1), 151; https://doi.org/10.3390/cells9010151 - 08 Jan 2020
Abstract
In order to ascertain their external environment, cells and tissues have the capability to sense and process a variety of stresses, including stretching and compression forces. These mechanical forces, as experienced by cells and tissues, are then converted into biochemical signals within the [...] Read more.
In order to ascertain their external environment, cells and tissues have the capability to sense and process a variety of stresses, including stretching and compression forces. These mechanical forces, as experienced by cells and tissues, are then converted into biochemical signals within the cell, leading to a number of cellular mechanisms being activated, including proliferation, differentiation and migration. If the conversion of mechanical cues into biochemical signals is perturbed in any way, then this can be potentially implicated in chronic disease development and processes such as neurological disorders, cancer and obesity. This review will focus on how the interplay between mechanotransduction, cellular structure, metabolism and signalling cascades led by the Hippo-YAP/TAZ axis can lead to a number of chronic diseases and suggest how we can target various pathways in order to design therapeutic targets for these debilitating diseases and conditions. Full article
(This article belongs to the Special Issue Mechanotransduction in Control of Cell Fate and Function)
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Open AccessReview
Mechanotransduction in the Cardiovascular System: From Developmental Origins to Homeostasis and Pathology
Cells 2019, 8(12), 1607; https://doi.org/10.3390/cells8121607 - 11 Dec 2019
Cited by 1
Abstract
With the term ‘mechanotransduction’, it is intended the ability of cells to sense and respond to mechanical forces by activating intracellular signal transduction pathways and the relative phenotypic adaptation. While a known role of mechanical stimuli has been acknowledged for developmental biology processes [...] Read more.
With the term ‘mechanotransduction’, it is intended the ability of cells to sense and respond to mechanical forces by activating intracellular signal transduction pathways and the relative phenotypic adaptation. While a known role of mechanical stimuli has been acknowledged for developmental biology processes and morphogenesis in various organs, the response of cells to mechanical cues is now also emerging as a major pathophysiology determinant. Cells of the cardiovascular system are typically exposed to a variety of mechanical stimuli ranging from compression to strain and flow (shear) stress. In addition, these cells can also translate subtle changes in biophysical characteristics of the surrounding matrix, such as the stiffness, into intracellular activation cascades with consequent evolution toward pro-inflammatory/pro-fibrotic phenotypes. Since cellular mechanotransduction has a potential readout on long-lasting modifications of the chromatin, exposure of the cells to mechanically altered environments may have similar persisting consequences to those of metabolic dysfunctions or chronic inflammation. In the present review, we highlight the roles of mechanical forces on the control of cardiovascular formation during embryogenesis, and in the development and pathogenesis of the cardiovascular system. Full article
(This article belongs to the Special Issue Mechanotransduction in Control of Cell Fate and Function)
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