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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Biology".

Deadline for manuscript submissions: closed (31 August 2020) | Viewed by 43083

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Prof. Dr. Sabata Martino

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Department of Chemistry, Biology and Biotechnology, Biochemistry and Molecular Biology Unit, University of Perugia, Via del Giochetto, 06126 Perugia, Italy
Interests: stem cell–biomaterial interaction; mecchanotransduction; stem cell reprogramming; gene/stem cell therapy; regenerative medicine; lysosomal storage disorders; neurodegenerative diseases
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Special Issue Information

Dear Colleagues,

The Special Issue “Mechanobiology in Cells and Tissues” will cover the most recent advances in the field of mechanobiology.

Mechanobiology refers to the study of the effects of physical forces in controlling cell functions. It has been demonstrated that the physical forces exerted by the cell microenvironment (e.g. extracellular matrix), are collected by the cytoskeleton components of cells and translated into biochemical signals that are transduced to the chromatin, which responds with changes in the genome conformation and in turn with a tailored gene expression signature. These signal cascades, called mechanotransduction, governs either the own cell functions, but also the tissue formation and tissue homeostasis. Alterations in such transduction mechanisms result in cell dysfunction and disease development (e.g. cancer, heart infarction, tissue degeneration).

The field of mechanobiology is multidisciplinary, since it covers many aspects of cell biology, molecular biology, physics, chemistry, and material science.

We invite authors to contribute original articles or comprehensive reviews.

Papers exploring mechanotransduction events in each of these areas are welcome:

-Mechanobiology and stem cells;

-Mechanobiology and tissue development;

-Mechanobiology and diseases (e.g. tissue degeneration; cancer);

-Mechanobiology and tissue engineering;

-Innovative techniques to study mechanobiology.

Prof. Sabata Martino
Guest Editor

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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. 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
physical forces
stiffness
gene reprogramming
biomaterials
tissue engineering
extracellular matrix

Published Papers (10 papers)

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Editorial

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4 pages, 205 KiB

Open AccessEditorial

Mechanobiology in Cells and Tissues

by Sabata Martino

Int. J. Mol. Sci. 2023, 24(10), 8564; https://doi.org/10.3390/ijms24108564 - 10 May 2023

Cited by 1 | Viewed by 1221

Abstract

This Editorial is a comment on the success of the Special Issue “Mechanobiology in Cells and Tissues” published in the International Journal of Molecular Sciences [...] Full article

(This article belongs to the Special Issue Mechanobiology in Cells and Tissues)

Research

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18 pages, 5710 KiB

Open AccessArticle

Hyaluronan Synthases’ Expression and Activity Are Induced by Fluid Shear Stress in Bone Marrow-Derived Mesenchymal Stem Cells

by Sebastian Reiprich, Elif Akova, Attila Aszódi and Veronika Schönitzer

Int. J. Mol. Sci. 2021, 22(6), 3123; https://doi.org/10.3390/ijms22063123 - 18 Mar 2021

Cited by 4 | Viewed by 2803

Abstract

During biomineralization, the cells generating the biominerals must be able to sense the external physical stimuli exerted by the growing mineralized tissue and change their intracellular protein composition according to these stimuli. In molluscan shell, the myosin-chitin synthases have been suggested to be the link for this communication between cells and the biomaterial. Hyaluronan synthases (HAS) belong to the same enzyme family as chitin synthases. Their product hyaluronan (HA) occurs in the bone and is supposed to have a regulatory function during bone regeneration. We hypothesize that HASes’ expression and activity are controlled by fluid-induced mechanotransduction as it is known for molluscan chitin synthases. In this study, bone marrow-derived human mesenchymal stem cells (hMSCs) were exposed to fluid shear stress of 10 Pa. The RNA transcriptome was analyzed by RNA sequencing (RNAseq). HA concentrations in the supernatants were measured by ELISA. The cellular structure of hMSCs and HAS2-overexpressing hMSCs was investigated after treatment with shear stress using confocal microscopy. Fluid shear stress upregulated the expression of genes that encode proteins belonging to the HA biosynthesis and bone mineralization pathways. The HAS activity appeared to be induced. Knowledge about the regulation mechanism governing HAS expression, trafficking, enzymatic activation and quality of the HA product in hMSCs is essential to understand the biological role of HA in the bone microenvironment. Full article

(This article belongs to the Special Issue Mechanobiology in Cells and Tissues)

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22 pages, 6549 KiB

Open AccessArticle

Shear Stress Modulates Osteoblast Cell and Nucleus Morphology and Volume

by Jianfeng Jin, Richard T. Jaspers, Gang Wu, Joannes A.M. Korfage, Jenneke Klein-Nulend and Astrid D. Bakker

Int. J. Mol. Sci. 2020, 21(21), 8361; https://doi.org/10.3390/ijms21218361 - 7 Nov 2020

Cited by 16 | Viewed by 3316

Abstract

Mechanical loading preserves bone mass and function—yet, little is known about the cell biological basis behind this preservation. For example, cell and nucleus morphology are critically important for cell function, but how these morphological characteristics are affected by the physiological mechanical loading of bone cells is under-investigated. This study aims to determine the effects of fluid shear stress on cell and nucleus morphology and volume of osteoblasts, and how these effects relate to changes in actin cytoskeleton and focal adhesion formation. Mouse calvaria 3T3-E1 (MC3T3-E1) osteoblasts were treated with or without 1 h pulsating fluid flow (PFF). Live-cell imaging was performed every 10 min during PFF and immediately after PFF. Cytoskeletal organization and focal adhesions were visualized, and gene and protein expression quantified. Two-dimensional (2D) and three-dimensional (3D) morphometric analyses were made using MeasureStack and medical imaging interaction toolkit (MITK) software. 2D-images revealed that 1 h PFF changed cell morphology from polygonal to triangular, and nucleus morphology from round to ellipsoid. PFF also reduced cell surface area (0.3-fold), cell volume (0.3-fold), and nucleus volume (0.2-fold). During PFF, the live-cell volume gradually decreased from 6000 to 3000 µm³. After PFF, α-tubulin orientation was more disorganized, but F-actin fluorescence intensity was enhanced, particularly around the nucleus. 3D-images obtained from Z-stacks indicated that PFF increased F-actin fluorescence signal distribution around the nucleus in the XZ and YZ direction (2.3-fold). PFF increased protein expression of phospho-paxillin (2.0-fold) and integrin-α5 (2.8-fold), but did not increase mRNA expression of paxillin-a (PXNA), paxillin-b (PXNB), integrin-α5 (ITGA51), or α-tubulin protein expression. In conclusion, PFF induced substantial changes in osteoblast cytoskeleton, as well as cell and nucleus morphology and volume, which was accompanied by elevated gene and protein expression of adhesion and structural proteins. More insights into the mechanisms whereby mechanical cues drive morphological changes in bone cells, and thereby, possibly in bone cell behavior, will aid the guidance of clinical treatment, particularly in the field of orthodontics, (oral) implantology, and orthopedics. Full article

(This article belongs to the Special Issue Mechanobiology in Cells and Tissues)

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15 pages, 2696 KiB

Open AccessArticle

Early Detection of Cartilage Degeneration: A Comparison of Histology, Fiber Bragg Grating-Based Micro-Indentation, and Atomic Force Microscopy-Based Nano-Indentation

by Bastian Hartmann, Gabriele Marchi, Paolo Alberton, Zsuzsanna Farkas, Attila Aszodi, Johannes Roths and Hauke Clausen-Schaumann

Int. J. Mol. Sci. 2020, 21(19), 7384; https://doi.org/10.3390/ijms21197384 - 6 Oct 2020

Cited by 18 | Viewed by 2925

Abstract

We have determined the sensitivity and detection limit of a new fiber Bragg grating (FBG)-based optoelectronic micro-indenter for biomechanical testing of cartilage and compared the results to indentation-type atomic force microscopy (IT-AFM) and histological staining. As test samples, we used bovine articular cartilage, which was enzymatically degraded ex vivo for five minutes using different concentrations of collagenase (5, 50, 100 and 500 µg/mL) to mimic moderate extracellular matrix deterioration seen in early-stage osteoarthritis (OA). Picrosirius Red staining and polarization microscopy demonstrated gradual, concentration-dependent disorganization of the collagen fibrillar network in the superficial zone of the explants. Osteoarthritis Research Society International (OARSI) grading of histopathological changes did not discriminate between undigested and enzymatically degraded explants. IT-AFM was the most sensitive method for detecting minute changes in cartilage biomechanics induced by the lowest collagenase concentration, however, it did not distinguish different levels of cartilage degeneration for collagenase concentrations higher than 5 µg/mL. The FBG micro-indenter provided a better and more precise assessment of the level of cartilage degeneration than the OARSI histological grading system but it was less sensitive at detecting mechanical changes than IT-AFM. The FBG-sensor allowed us to observe differences in cartilage biomechanics for collagenase concentrations of 100 and 500 µg/mL. Our results confirm that the FBG sensor is capable of detecting small changes in articular cartilage stiffness, which may be associated with initial cartilage degeneration caused by early OA. Full article

(This article belongs to the Special Issue Mechanobiology in Cells and Tissues)

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16 pages, 2111 KiB

Open AccessArticle

Pressure Stimuli Improve the Proliferation of Wharton’s Jelly-Derived Mesenchymal Stem Cells under Hypoxic Culture Conditions

by Sang Eon Park, Hyeongseop Kim, Soojin Kwon, Suk-joo Choi, Soo-young Oh, Gyu Ha Ryu, Hong Bae Jeon and Jong Wook Chang

Int. J. Mol. Sci. 2020, 21(19), 7092; https://doi.org/10.3390/ijms21197092 - 25 Sep 2020

Cited by 8 | Viewed by 2507

Abstract

Mesenchymal stem cells (MSCs) are safe, and they have good therapeutic efficacy through their paracrine action. However, long-term culture to produce sufficient MSCs for clinical use can result in side-effects, such as an inevitable senescence and the reduction of the therapeutic efficacy of the MSCs. In order to overcome this, the primary culture conditions of the MSCs can be modified to simulate the stem cells’ niche environment, resulting in accelerated proliferation, the achievement of the target production yield at earlier passages, and the improvement of the therapeutic efficacy. We exposed Wharton’s jelly-derived MSCs (WJ-MSCs) to pressure stimuli during the primary culture step. In order to evaluate the proliferation, stemness, and therapeutic efficacy of WJ-MSCs, image, genetic, and Western blot analyses were carried out. Compared with standard incubation culture conditions, the cell proliferation was significantly improved when the WJ-MSCs were exposed to pressure stimuli. However, the therapeutic efficacy (the promotion of cell proliferation and anti-apoptotic effects) and the stemness of the WJ-MSCs was maintained, regardless of the culture conditions. Exposure to pressure stimuli is a simple and efficient way to improve WJ-MSC proliferation without causing changes in stemness and therapeutic efficacy. In this way, clinical-grade WJ-MSCs can be produced rapidly and used for therapeutic applications. Full article

(This article belongs to the Special Issue Mechanobiology in Cells and Tissues)

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35 pages, 7813 KiB

Open AccessArticle

Dissecting the Effect of a 3D Microscaffold on the Transcriptome of Neural Stem Cells with Computational Approaches: A Focus on Mechanotransduction

by Federica Rey, Cecilia Pandini, Bianca Barzaghini, Letizia Messa, Toniella Giallongo, Orietta Pansarasa, Stella Gagliardi, Matteo Brilli, Gian Vincenzo Zuccotti, Cristina Cereda, Manuela Teresa Raimondi and Stephana Carelli

Int. J. Mol. Sci. 2020, 21(18), 6775; https://doi.org/10.3390/ijms21186775 - 15 Sep 2020

Cited by 9 | Viewed by 2729

Abstract

3D cell cultures are becoming more and more important in the field of regenerative medicine due to their ability to mimic the cellular physiological microenvironment. Among the different types of 3D scaffolds, we focus on the Nichoid, a miniaturized scaffold with a structure inspired by the natural staminal niche. The Nichoid can activate cellular responses simply by subjecting the cells to mechanical stimuli. This kind of influence results in different cellular morphology and organization, but the molecular bases of these changes remain largely unknown. Through RNA-Seq approach on murine neural precursors stem cells expanded inside the Nichoid, we investigated the deregulated genes and pathways showing that the Nichoid causes alteration in genes strongly connected to mechanobiological functions. Moreover, we fully dissected this mechanism highlighting how the changes start at a membrane level, with subsequent alterations in the cytoskeleton, signaling pathways, and metabolism, all leading to a final alteration in gene expression. The results shown here demonstrate that the Nichoid influences the biological and genetic response of stem cells thorough specific alterations of cellular signaling. The characterization of these pathways elucidates the role of mechanical manipulation on stem cells, with possible implications in regenerative medicine applications. Full article

(This article belongs to the Special Issue Mechanobiology in Cells and Tissues)

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Review

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17 pages, 1969 KiB

Open AccessReview

Peripheral Mechanobiology of Touch—Studies on Vertebrate Cutaneous Sensory Corpuscles

by Ramón Cobo, Jorge García-Piqueras, Yolanda García-Mesa, Jorge Feito, Olivia García-Suárez and Jose A Vega

Int. J. Mol. Sci. 2020, 21(17), 6221; https://doi.org/10.3390/ijms21176221 - 27 Aug 2020

Cited by 21 | Viewed by 8098

Abstract

The vertebrate skin contains sensory corpuscles that are receptors for different qualities of mechanosensitivity like light brush, touch, pressure, stretch or vibration. These specialized sensory organs are linked anatomically and functionally to mechanosensory neurons, which function as low-threshold mechanoreceptors connected to peripheral skin through Aβ nerve fibers. Furthermore, low-threshold mechanoreceptors associated with Aδ and C nerve fibers have been identified in hairy skin. The process of mechanotransduction requires the conversion of a mechanical stimulus into electrical signals (action potentials) through the activation of mechanosensible ion channels present both in the axon and the periaxonal cells of sensory corpuscles (i.e., Schwann-, endoneurial- and perineurial-related cells). Most of those putative ion channels belong to the degenerin/epithelial sodium channel (especially the family of acid-sensing ion channels), the transient receptor potential channel superfamilies, and the Piezo family. This review updates the current data about the occurrence and distribution of putative mechanosensitive ion channels in cutaneous mechanoreceptors including primary sensory neurons and sensory corpuscles. Full article

(This article belongs to the Special Issue Mechanobiology in Cells and Tissues)

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20 pages, 2899 KiB

Open AccessReview

Recent Advances in Mechanically Loaded Human Mesenchymal Stem Cells for Bone Tissue Engineering

by Kar Wey Yong, Jane Ru Choi, Jean Yu Choi and Alistair C. Cowie

Int. J. Mol. Sci. 2020, 21(16), 5816; https://doi.org/10.3390/ijms21165816 - 13 Aug 2020

Cited by 30 | Viewed by 3436

Abstract

Large bone defects are a major health concern worldwide. The conventional bone repair techniques (e.g., bone-grafting and Masquelet techniques) have numerous drawbacks, which negatively impact their therapeutic outcomes. Therefore, there is a demand to develop an alternative bone repair approach that can address the existing drawbacks. Bone tissue engineering involving the utilization of human mesenchymal stem cells (hMSCs) has recently emerged as a key strategy for the regeneration of damaged bone tissues. However, the use of tissue-engineered bone graft for the clinical treatment of bone defects remains challenging. While the role of mechanical loading in creating a bone graft has been well explored, the effects of mechanical loading factors (e.g., loading types and regime) on clinical outcomes are poorly understood. This review summarizes the effects of mechanical loading on hMSCs for bone tissue engineering applications. First, we discuss the key assays for assessing the quality of tissue-engineered bone grafts, including specific staining, as well as gene and protein expression of osteogenic markers. Recent studies of the impact of mechanical loading on hMSCs, including compression, perfusion, vibration and stretching, along with the potential mechanotransduction signalling pathways, are subsequently reviewed. Lastly, we discuss the challenges and prospects of bone tissue engineering applications. Full article

(This article belongs to the Special Issue Mechanobiology in Cells and Tissues)

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33 pages, 4442 KiB

Open AccessReview

Insight into Mechanobiology: How Stem Cells Feel Mechanical Forces and Orchestrate Biological Functions

by Chiara Argentati, Francesco Morena, Ilaria Tortorella, Martina Bazzucchi, Serena Porcellati, Carla Emiliani and Sabata Martino

Int. J. Mol. Sci. 2019, 20(21), 5337; https://doi.org/10.3390/ijms20215337 - 26 Oct 2019

Cited by 77 | Viewed by 10335

Abstract

The cross-talk between stem cells and their microenvironment has been shown to have a direct impact on stem cells’ decisions about proliferation, growth, migration, and differentiation. It is well known that stem cells, tissues, organs, and whole organisms change their internal architecture and composition in response to external physical stimuli, thanks to cells’ ability to sense mechanical signals and elicit selected biological functions. Likewise, stem cells play an active role in governing the composition and the architecture of their microenvironment. Is now being documented that, thanks to this dynamic relationship, stemness identity and stem cell functions are maintained. In this work, we review the current knowledge in mechanobiology on stem cells. We start with the description of theoretical basis of mechanobiology, continue with the effects of mechanical cues on stem cells, development, pathology, and regenerative medicine, and emphasize the contribution in the field of the development of ex-vivo mechanobiology modelling and computational tools, which allow for evaluating the role of forces on stem cell biology. Full article

(This article belongs to the Special Issue Mechanobiology in Cells and Tissues)

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12 pages, 927 KiB

Open AccessReview

Polycystins and Mechanotransduction in Human Disease

by Antonios N. Gargalionis, Efthimia K. Basdra and Athanasios G. Papavassiliou

Int. J. Mol. Sci. 2019, 20(9), 2182; https://doi.org/10.3390/ijms20092182 - 2 May 2019

Cited by 20 | Viewed by 4223

Abstract

Alterations in the process of mechanotransduction have been implicated in the pathogenesis of several diseases such as genetic diseases, osteoporosis, cardiovascular anomalies, and cancer. Several studies over the past twenty years have demonstrated that polycystins (polycystin-1, PC1; and polycystin-2, PC2) respond to changes of extracellular mechanical cues, and mediate pathogenic mechanotransduction and cyst formation in kidney cells. However, recent reports reveal the emergence of polycystins as key proteins that facilitate the transduction of mechano-induced signals in various clinical entities besides polycystic kidney disease, such as cancer, cardiovascular defects, bone loss, and deformations, as well as inflammatory processes like psoriasis. Herewith, we discuss data from recent studies that establish this role with potential clinical utility. Full article

(This article belongs to the Special Issue Mechanobiology in Cells and Tissues)

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