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Physical Energies and Morphogenetic Signaling
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Physical Energies and Morphogenetic Signaling

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

Deadline for manuscript submissions: closed (20 November 2022) | Viewed by 16855

Special Issue Editor

Prof. Dr. Carlo Ventura

E-Mail Website
Guest Editor
Department of Medical and Surgical Sciences, School of Medicine, University of Bologna, Via G. Massarenti 9, 40138 Bologna, Italy
Interests: human mesenchymal stem cells; physical energies; regenerative medicine
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Understanding how biological information is shaped from the nanoscale level of molecular/supramolecular interactions to the subcellular and cellular level, up to the pattern control of large-scale anatomy and morphogenesis is currently posing a number of unanswered questions, and boosting novel strategies for regenerative and precision medicine.

The field of stem cell biology is evolving in parallel with our understanding of mechanobiology and cellular mechanosensing, and the compelling evidence that stem cells are also finely tuned by physical energies, including mechanical vibrations, bioelectricity, magnetic fields and light.

Compounding the complexity of this picture, cellular responses to physical stimulation have been shown to remarkably vary in their quality and extent depending on whether the same stimulus was sent in a continuous or pulsed fashion. Within the pulsed modality, a multifaceted (stem)cell behavior emerged based upon the frequency and the interval composition patterning of exposure. On these bases, we are becoming aware that (stem)cells are also able to afford computational tasks transforming electromagnetic inputs, including light radiation, into a mechanical signaling, and viceversa.

Unveiling the morphogenetic code that cells are using to compose the symphony of a software of Life, orchestrating the hardware of cellular genome and biomolecular signaling is still at an early stage. Only recently researchers are resuming seminal discoveries from pioneering studies, approaching a challenging scientific endeavor to shift understanding of biophysical signaling from a punctual level (i.e. a biophysical dissection of individual players at targeted subcellular locations) to a wider interconnected picture. Boosting this transition process holds promise for deciphering the complex dynamics through which physical forces and molecular cues concur in shaping a morphogenetic code. Hopefully, in a near future this path may lead to the development of unprecedented tools to afford delivery of defined, and well-characterized electro-magnetic- or electro-mechanical stimuli in confined tissues to overcome diseased states, including malignancies, and boost our inherent self-healing potential.

This Special Issue aims at providing a platform for basic and translational science, publishing innovative research and review articles contributed by eminent Scientists who have been using physical energies, including electromagnetic fields, light and mechanical vibrations, eventually exploiting the growing development in electronics and artificial intelligence (AI), to target (stem)cell/tissue morphogenesis and regenerative potential.

Authors’ contributions are not restricted to a particular field of morphogenesis and regeneration, and can also span through all models of degenerative diseases, including malignant transformation and rescue.

Prof. Dr. Carlo Ventura
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.

Published Papers (7 papers)

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Research

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15 pages, 4417 KiB  
Article
Wavelength-Dependent Effects of Photobiomodulation for Wound Care in Diabetic Wounds
by Peter Dungel, Sanja Sutalo, Cyrill Slezak, Claudia Keibl, Barbara Schädl, Harald Schnidar, Magdalena Metzger, Barbara Meixner, Jaana Hartmann, Johannes Oesterreicher, Heinz Redl and Paul Slezak
Int. J. Mol. Sci. 2023, 24(6), 5895; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms24065895 - 20 Mar 2023
Cited by 2 | Viewed by 3655
Abstract
Photobiomodulation, showing positive effects on wound healing processes, has been performed mainly with lasers in the red/infrared spectrum. Light of shorter wavelengths can significantly influence biological systems. This study aimed to evaluate and compare the therapeutic effects of pulsed LED light of different [...] Read more.
Photobiomodulation, showing positive effects on wound healing processes, has been performed mainly with lasers in the red/infrared spectrum. Light of shorter wavelengths can significantly influence biological systems. This study aimed to evaluate and compare the therapeutic effects of pulsed LED light of different wavelengths on wound healing in a diabetic (db/db) mouse excision wound model. LED therapy by Repuls was applied at either 470 nm (blue), 540 nm (green) or 635 nm (red), at 40 mW/cm2 each. Wound size and wound perfusion were assessed and correlated to wound temperature and light absorption in the tissue. Red and trend-wise green light positively stimulated wound healing, while blue light was ineffective. Light absorption was wavelength-dependent and was associated with significantly increased wound perfusion as measured by laser Doppler imaging. Shorter wavelengths ranging from green to blue significantly increased wound surface temperature, while red light, which penetrates deeper into tissue, led to a significant increase in core body temperature. In summary, wound treatment with pulsed red or green light resulted in improved wound healing in diabetic mice. Since impeded wound healing in diabetic patients poses an ever-increasing socio-economic problem, LED therapy may be an effective, easily applied and cost-efficient supportive treatment for diabetic wound therapy. Full article
(This article belongs to the Special Issue Physical Energies and Morphogenetic Signaling)
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20 pages, 4202 KiB  
Article
Information Theory as an Experimental Tool for Integrating Disparate Biophysical Signaling Modules
by Patrick McMillen, Sara I. Walker and Michael Levin
Int. J. Mol. Sci. 2022, 23(17), 9580; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23179580 - 24 Aug 2022
Cited by 3 | Viewed by 2319
Abstract
There is a growing appreciation in the fields of cell biology and developmental biology that cells collectively process information in time and space. While many powerful molecular tools exist to observe biophysical dynamics, biologists must find ways to quantitatively understand these phenomena at [...] Read more.
There is a growing appreciation in the fields of cell biology and developmental biology that cells collectively process information in time and space. While many powerful molecular tools exist to observe biophysical dynamics, biologists must find ways to quantitatively understand these phenomena at the systems level. Here, we present a guide for the application of well-established information theory metrics to biological datasets and explain these metrics using examples from cell, developmental and regenerative biology. We introduce a novel computational tool named after its intended purpose, calcium imaging, (CAIM) for simple, rigorous application of these metrics to time series datasets. Finally, we use CAIM to study calcium and cytoskeletal actin information flow patterns between Xenopus laevis embryonic animal cap stem cells. The tools that we present here should enable biologists to apply information theory to develop a systems-level understanding of information processing across a diverse array of experimental systems. Full article
(This article belongs to the Special Issue Physical Energies and Morphogenetic Signaling)
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15 pages, 3813 KiB  
Article
Shockwaves Increase In Vitro Resilience of Rhizopus oryzae Biofilm under Amphotericin B Treatment
by Cyrill Slezak, Karaleen Anderson, Tyson Hillock, Mariel Miller, Peter Dungel, Olga Kopp, Katja Sterflinger and Paul Slezak
Int. J. Mol. Sci. 2022, 23(16), 9226; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23169226 - 17 Aug 2022
Viewed by 1506
Abstract
Acoustical biophysical therapies, including ultrasound, radial pressure waves, and shockwaves, have been shown to harbor both a destructive and regenerative potential depending on physical treatment parameters. Despite the clinical relevance of fungal biofilms, little work exits comparing the efficacy of these modalities on [...] Read more.
Acoustical biophysical therapies, including ultrasound, radial pressure waves, and shockwaves, have been shown to harbor both a destructive and regenerative potential depending on physical treatment parameters. Despite the clinical relevance of fungal biofilms, little work exits comparing the efficacy of these modalities on the destruction of fungal biofilms. This study evaluates the impact of acoustical low-frequency ultrasound, radial pressure waves, and shockwaves on the viability and proliferation of in vitro Rhizopus oryzae biofilm under Amphotericin B induced apoptosis. In addition, the impact of a fibrin substrate in comparison with a traditional polystyrene well-plate one is explored. We found consistent, mechanically promoted increased Amphotericin B efficacy when treating the biofilm in conjunction with low frequency ultrasound and radial pressure waves. In contrast, shockwave induced effects of mechanotransduction results in a stronger resilience of the biofilm, which was evident by a marked increase in cellular viability, and was not observed in the other types of acoustical pressure waves. Our findings suggest that fungal biofilms not only provide another model for mechanistical investigations of the regenerative properties of shockwave therapies, but warrant future investigations into the clinical viability of the therapy. Full article
(This article belongs to the Special Issue Physical Energies and Morphogenetic Signaling)
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16 pages, 3148 KiB  
Article
Physical Considerations for In Vitro ESWT Research Design
by Cyrill Slezak, Roland Rose, Julia M. Jilge, Robert Nuster, David Hercher and Paul Slezak
Int. J. Mol. Sci. 2022, 23(1), 313; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23010313 - 28 Dec 2021
Cited by 2 | Viewed by 1782
Abstract
In vitro investigations, which comprise the bulk of research efforts geared at identifying an underlying biomechanical mechanism for extracorporeal shock wave therapy (ESWT), are commonly hampered by inadequate descriptions of the underlying therapeutic acoustical pressure waves. We demonstrate the necessity of in-situ sound [...] Read more.
In vitro investigations, which comprise the bulk of research efforts geared at identifying an underlying biomechanical mechanism for extracorporeal shock wave therapy (ESWT), are commonly hampered by inadequate descriptions of the underlying therapeutic acoustical pressure waves. We demonstrate the necessity of in-situ sound pressure measurements inside the treated samples considering the significant differences associated with available applicator technologies and cell containment. A statistical analysis of pulse-to-pulse variability in an electrohydraulic applicator yields a recommendation for a minimal pulse number of n = 300 for cell pallets and suspensions to achieve reproducible treatments. Non-linear absorption behavior of sample holders and boundary effects are shown for transient peak pressures and applied energies and may serve as a guide when in-situ measurements are not available or can be used as a controllable experimental design factor. For the use in microbiological investigations of ESWT we provide actionable identification of common problems in describing physical shockwave parameters and improving experimental setups by; (1) promoting in-situ sound field measurements, (2) statistical evaluation of applicator variability, and (3) extrapolation of treatment parameters based on focal and treatment volumes. Full article
(This article belongs to the Special Issue Physical Energies and Morphogenetic Signaling)
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14 pages, 5203 KiB  
Article
Wnt Modulation Enhances Otic Differentiation by Facilitating the Enucleation Process but Develops Unnecessary Cardiac Structures
by Nathaniel T. Carpena, So-Young Chang, Ji-Eun Choi, Jae Yun Jung and Min Young Lee
Int. J. Mol. Sci. 2021, 22(19), 10306; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms221910306 - 24 Sep 2021
Cited by 6 | Viewed by 2309
Abstract
Otic organoids have the potential to resolve current challenges in hearing loss research. The reproduction of the delicate and complex structure of the mammalian cochlea using organoids requires high efficiency and specificity. Recent attempts to strengthen otic organoids have focused on the effects [...] Read more.
Otic organoids have the potential to resolve current challenges in hearing loss research. The reproduction of the delicate and complex structure of the mammalian cochlea using organoids requires high efficiency and specificity. Recent attempts to strengthen otic organoids have focused on the effects of the Wnt signaling pathway on stem cell differentiation. One important aspect of this is the evaluation of undesirable effects of differentiation after Wnt activation. In the present study, we differentiated mouse embryonic stem cell embryoid bodies (EB) into otic organoids and observed two morphologies with different cell fates. EBs that underwent a core ejection process, or ‘enucleation,’ were similar to previously reported inner ear organoids. Meanwhile, EBs that retained their core demonstrated features characteristic of neural organoids. The application of a Wnt agonist during the maturation phase increased enucleation, as well as otic organoid formation, in turn leading to sensory hair cell-like cell generation. However, with a longer incubation period, Wnt activation also led to EBs with ‘beating’ organoids that exhibited spontaneous movement. This observation emphasizes the necessity of optimizing Wnt enhancement for the differentiation of specific cells, such as those found in the inner ear. Full article
(This article belongs to the Special Issue Physical Energies and Morphogenetic Signaling)
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Review

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19 pages, 76560 KiB  
Review
Stimulation of Chondrogenesis in a Developmental Model of Endochondral Bone Formation by Pulsed Electromagnetic Fields
by Jake Littman and Roy K. Aaron
Int. J. Mol. Sci. 2023, 24(4), 3275; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms24043275 - 07 Feb 2023
Cited by 2 | Viewed by 1203
Abstract
Notable characteristics of the skeleton are its responsiveness to physical stimuli and its ability to remodel secondary to changing biophysical environments and thereby fulfill its physiological roles of stability and movement. Bone and cartilage cells have many mechanisms to sense physical cues and [...] Read more.
Notable characteristics of the skeleton are its responsiveness to physical stimuli and its ability to remodel secondary to changing biophysical environments and thereby fulfill its physiological roles of stability and movement. Bone and cartilage cells have many mechanisms to sense physical cues and activate a variety of genes to synthesize structural molecules to remodel their extracellular matrix and soluble molecules for paracrine signaling. This review describes the response of a developmental model of endochondral bone formation which is translationally relevant to embryogenesis, growth, and repair to an externally applied pulsed electromagnetic field (PEMF). The use of a PEMF allows for the exploration of morphogenesis in the absence of distracting stimuli such as mechanical load and fluid flow. The response of the system is described in terms of the cell differentiation and extracellular matrix synthesis in chondrogenesis. Emphasis is placed upon dosimetry of the applied physical stimulus and some of the mechanisms of tissue response through a developmental process of maturation. PEMFs are used clinically for bone repair and have other potential clinical applications. These features of tissue response and signal dosimetry can be extrapolated to the design of clinically optimal stimulation. Full article
(This article belongs to the Special Issue Physical Energies and Morphogenetic Signaling)
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23 pages, 11635 KiB  
Review
Cell Responsiveness to Physical Energies: Paving the Way to Decipher a Morphogenetic Code
by Riccardo Tassinari, Claudia Cavallini, Elena Olivi, Federica Facchin, Valentina Taglioli, Chiara Zannini, Martina Marcuzzi and Carlo Ventura
Int. J. Mol. Sci. 2022, 23(6), 3157; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23063157 - 15 Mar 2022
Cited by 3 | Viewed by 2804
Abstract
We discuss emerging views on the complexity of signals controlling the onset of biological shapes and functions, from the nanoarchitectonics arising from supramolecular interactions, to the cellular/multicellular tissue level, and up to the unfolding of complex anatomy. We highlight the fundamental role of [...] Read more.
We discuss emerging views on the complexity of signals controlling the onset of biological shapes and functions, from the nanoarchitectonics arising from supramolecular interactions, to the cellular/multicellular tissue level, and up to the unfolding of complex anatomy. We highlight the fundamental role of physical forces in cellular decisions, stressing the intriguing similarities in early morphogenesis, tissue regeneration, and oncogenic drift. Compelling evidence is presented, showing that biological patterns are strongly embedded in the vibrational nature of the physical energies that permeate the entire universe. We describe biological dynamics as informational processes at which physics and chemistry converge, with nanomechanical motions, and electromagnetic waves, including light, forming an ensemble of vibrations, acting as a sort of control software for molecular patterning. Biomolecular recognition is approached within the establishment of coherent synchronizations among signaling players, whose physical nature can be equated to oscillators tending to the coherent synchronization of their vibrational modes. Cytoskeletal elements are now emerging as senders and receivers of physical signals, “shaping” biological identity from the cellular to the tissue/organ levels. We finally discuss the perspective of exploiting the diffusive features of physical energies to afford in situ stem/somatic cell reprogramming, and tissue regeneration, without stem cell transplantation. Full article
(This article belongs to the Special Issue Physical Energies and Morphogenetic Signaling)
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