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Article ; Online: Editorial for The Nanoengineering for Mechanobiology (N4M) symposium.

Di Russo, Jacopo / Ferrari, Aldo / Vassalli, Massimo

Biomaterials advances

2023 Volume 156, Page(s) 213706

MeSH term(s)	Chondrocytes ; Biomechanical Phenomena ; Biophysics
Language	English
Publishing date	2023-11-28
Publishing country	Netherlands
Document type	Editorial
ISSN	2772-9508
ISSN (online)	2772-9508
DOI	10.1016/j.bioadv.2023.213706
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Article ; Online: A keratin code defines the textile nature of epithelial tissue architecture.

Di Russo, Jacopo / Magin, Thomas M / Leube, Rudolf E

Current opinion in cell biology

2023 Volume 85, Page(s) 102236

Abstract: We suggest that the human body can be viewed as of textile nature whose fabric consists of interconnected fiber systems. These fiber systems form highly dynamic scaffolds, which respond to environmental changes at different temporal and spatial scales. ... ...

Abstract	We suggest that the human body can be viewed as of textile nature whose fabric consists of interconnected fiber systems. These fiber systems form highly dynamic scaffolds, which respond to environmental changes at different temporal and spatial scales. This is especially relevant at sites where epithelia border on connective tissue regions that are exposed to dynamic microenvironments. We propose that the enormous heterogeneity and adaptability of epithelia are based on a "keratin code", which results from the cell-specific expression and posttranslational modification of keratin isotypes. It thereby defines unique cytoskeletal intermediate filament networks that are coupled across cells and to the correspondingly heterogeneous fibers of the underlying extracellular matrix. The resulting fabric confers unique local properties.
MeSH term(s)	Humans ; Keratins/metabolism ; Cytoskeleton/metabolism ; Epithelium/metabolism ; Intermediate Filaments/metabolism ; Textiles
Chemical Substances	Keratins (68238-35-7)
Language	English
Publishing date	2023-09-12
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	1026381-0
ISSN	1879-0410 ; 0955-0674
ISSN (online)	1879-0410
ISSN	0955-0674
DOI	10.1016/j.ceb.2023.102236
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Article ; Online: Mechanobiological implications of age-related remodelling in the outer retina.

Piskova, Teodora / Kozyrina, Aleksandra N / Di Russo, Jacopo

Biomaterials advances

2023 Volume 147, Page(s) 213343

Abstract: The outer retina consists of the light-sensitive photoreceptors, the pigmented epithelium, and the choroid, which interact in a complex manner to sustain homeostasis. The organisation and function of these cellular layers are mediated by the ... ...

Abstract	The outer retina consists of the light-sensitive photoreceptors, the pigmented epithelium, and the choroid, which interact in a complex manner to sustain homeostasis. The organisation and function of these cellular layers are mediated by the extracellular matrix compartment named Bruch's membrane, situated between the retinal epithelium and the choroid. Like many tissues, the retina experiences age-related structural and metabolic changes, which are relevant for understanding major blinding diseases of the elderly, such as age-related macular degeneration. Compared with other tissues, the retina mainly comprises postmitotic cells, making it less able to maintain its mechanical homeostasis over the years functionally. Aspects of retinal ageing, like the structural and morphometric changes of the pigment epithelium and the heterogenous remodelling of the Bruch's membrane, imply changes in tissue mechanics and may affect functional integrity. In recent years, findings in the field of mechanobiology and bioengineering highlighted the importance of mechanical changes in tissues for understanding physiological and pathological processes. Here, we review the current knowledge of age-related changes in the outer retina from a mechanobiological perspective, aiming to generate food for thought for future mechanobiology studies in the outer retina.
MeSH term(s)	Humans ; Aged ; Pigment Epithelium of Eye/metabolism ; Pigment Epithelium of Eye/pathology ; Retina/metabolism ; Retina/pathology ; Choroid/metabolism ; Choroid/pathology ; Bruch Membrane/metabolism ; Bruch Membrane/pathology ; Macular Degeneration/metabolism ; Macular Degeneration/pathology
Language	English
Publishing date	2023-02-15
Publishing country	Netherlands
Document type	Review ; Journal Article
ISSN	2772-9508
ISSN (online)	2772-9508
DOI	10.1016/j.bioadv.2023.213343
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Article: Why does epithelia display heterogeneity? Bridging physical and biological concepts.

Vishwakarma, Medhavi / Di Russo, Jacopo

Biophysical reviews

2019 Volume 11, Issue 5, Page(s) 683–687

Language	English
Publishing date	2019-09-07
Publishing country	Germany
Document type	Letter
ZDB-ID	2486483-3
ISSN	1867-2469 ; 1867-2450
ISSN (online)	1867-2469
ISSN	1867-2450
DOI	10.1007/s12551-019-00583-6
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Article: Mechanobiology of Epithelia From the Perspective of Extracellular Matrix Heterogeneity.

Kozyrina, Aleksandra N / Piskova, Teodora / Di Russo, Jacopo

Frontiers in bioengineering and biotechnology

2020 Volume 8, Page(s) 596599

Abstract: Understanding the complexity of the extracellular matrix (ECM) and its variability is a necessary step on the way to engineering functional (bio)materials that serve their respective purposes while relying on cell adhesion. Upon adhesion, cells receive ... ...

Abstract	Understanding the complexity of the extracellular matrix (ECM) and its variability is a necessary step on the way to engineering functional (bio)materials that serve their respective purposes while relying on cell adhesion. Upon adhesion, cells receive messages which contain both biochemical and mechanical information. The main focus of mechanobiology lies in investigating the role of this mechanical coordination in regulating cellular behavior. In recent years, this focus has been additionally shifted toward cell collectives and the understanding of their behavior as a whole mechanical continuum. Collective cell phenomena very much apply to epithelia which are either simple cell-sheets or more complex three-dimensional structures. Researchers have been mostly using the organization of monolayers to observe their collective behavior in well-defined experimental setups
Language	English
Publishing date	2020-11-20
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2719493-0
ISSN	2296-4185
ISSN	2296-4185
DOI	10.3389/fbioe.2020.596599
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Article ; Online: Symptomatic androgen deficiency and sexual dysfunctions in male patients receiving alectinib for ALK-positive advanced nonsmall cell lung cancer.

Vita, Emanuele / Monaca, Federico / Milardi, Domenico / Mastrantoni, Luca / Stefani, Alessio / Vergani, Edoardo / Russo, Jacopo / Barone, Diletta / Sparagna, Ileana / Vitale, Antonio / Scala, Alessandro / Occhipinti, Denis / Di Salvatore, Mariantonietta / Pontecorvi, Alfredo / Tortora, Giampaolo / Bria, Emilio

Cancer

2024

Abstract: Background: It is reported that treatment with anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs) induces hypogonadism both in male patients with ALK-positive cancer and in murine models.: Methods: In this study, three groups, ... ...

Abstract	Background: It is reported that treatment with anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs) induces hypogonadism both in male patients with ALK-positive cancer and in murine models. Methods: In this study, three groups, including an experimental group of male patients with ALK-positive, advanced nonsmall cell lung cancer (ANSCLC) who were receiving alectinib (cohort A), a control group of female patients with ALK-positive ANSCLC who were receiving alectinib (cohort B), and a control group of male patients with ALK-negative ANSCLC (cohort C), prospectively underwent a full hormone assessment for androgen deficiency at 8 weeks after the start of treatment and in case of reported suspected symptoms. Patients with major sexual dysfunctions were referred to an endocrinologist. Results: Ninety-five patients were consecutively enrolled onto the study. Among sixty-eight male patients, both median total testosterone levels (2.93 vs. 4.92 ng/ml; p = .0001) and free testosterone levels (0.11 vs. 0.17 pg/ml; p = .0002) were significantly lower in ALK-positive ANSCLC patients in cohort A compared with ALK-negative patients in cohort C; conversely, median FSH (10.32 vs. 17.52 mUI/ml; p = .0059) and LH levels (4.72 vs. 7.49 mUI/ml; p = .0131) were significantly higher in cohort C compared to cohort A. Median inhibin B levels were higher in ALK-positive male patients (74.3 vs. 44.24 pg/ml; p = .0038), but all patients had inhibin B values within the normal range. The percentage of male patients who had positive scores on the Androgen Deficiency in Aging Males (ADAM) questionnaire was 62% in cohort A and 26.8% in cohort C, including eight patients who reported at least one major symptom and were referred to Andrology Unit. No significant differences in the endocrine assessment were reported between cohorts A and B. Conclusions: Symptoms of androgen deficiency should be tracked in male patients with ALK-positive ANSCLC who are receiving alectinib, and testosterone replacement should be considered, as appropriate.
Language	English
Publishing date	2024-03-28
Publishing country	United States
Document type	Journal Article
ZDB-ID	1429-1
ISSN	1097-0142 ; 0008-543X ; 1934-662X
ISSN (online)	1097-0142
ISSN	0008-543X ; 1934-662X
DOI	10.1002/cncr.35293
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Article: Combining Image Restoration and Traction Force Microscopy to Study Extracellular Matrix-Dependent Keratin Filament Network Plasticity.

Yoon, Sungjun / Windoffer, Reinhard / Kozyrina, Aleksandra N / Piskova, Teodora / Di Russo, Jacopo / Leube, Rudolf E

Frontiers in cell and developmental biology

2022 Volume 10, Page(s) 901038

Abstract: Keratin intermediate filaments are dynamic cytoskeletal components that are responsible for tuning the mechanical properties of epithelial tissues. Although it is known that keratin filaments (KFs) are able to sense and respond to changes in the ... ...

Abstract	Keratin intermediate filaments are dynamic cytoskeletal components that are responsible for tuning the mechanical properties of epithelial tissues. Although it is known that keratin filaments (KFs) are able to sense and respond to changes in the physicochemical properties of the local niche, a direct correlation of the dynamic three-dimensional network structure at the single filament level with the microenvironment has not been possible. Using conventional approaches, we find that keratin flow rates are dependent on extracellular matrix (ECM) composition but are unable to resolve KF network organization at the single filament level in relation to force patterns. We therefore developed a novel method that combines a machine learning-based image restoration technique and traction force microscopy to decipher the fine details of KF network properties in living cells grown on defined ECM patterns. Our approach utilizes Content-Aware Image Restoration (CARE) to enhance the temporal resolution of confocal fluorescence microscopy by at least five fold while preserving the spatial resolution required for accurate extraction of KF network structure at the single KF/KF bundle level. The restored images are used to segment the KF network, allowing numerical analyses of its local properties. We show that these tools can be used to study the impact of ECM composition and local mechanical perturbations on KF network properties and corresponding traction force patterns in size-controlled keratinocyte assemblies. We were thus able to detect increased curvature but not length of KFs on laminin-322 versus fibronectin. Photoablation of single cells in microprinted circular quadruplets revealed surprisingly little but still significant changes in KF segment length and curvature that were paralleled by an overall reduction in traction forces without affecting global network orientation in the modified cell groups irrespective of the ECM coating. Single cell analyses furthermore revealed differential responses to the photoablation that were less pronounced on laminin-332 than on fibronectin. The obtained results illustrate the feasibility of combining multiple techniques for multimodal monitoring and thereby provide, for the first time, a direct comparison between the changes in KF network organization at the single filament level and local force distribution in defined paradigms.
Language	English
Publishing date	2022-05-11
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2737824-X
ISSN	2296-634X
ISSN	2296-634X
DOI	10.3389/fcell.2022.901038
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Article ; Online: Exposure of Buffalo Milkers to Pathogenic Bacteria and Characterization of Isolated Methicillin-Resistant

Carraturo, Federica / Alterisio, Maria Chiara / Guccione, Jacopo / Cerullo, Valeria / Salamone, Michela / Morelli, Michela / Libralato, Giovanni / Russo, Ernesto / d'Angelo, Raffaele / Ciaramella, Paolo / Di Loria, Antonio / Guida, Marco

International journal of environmental research and public health

2022 Volume 19, Issue 7

Abstract: The research was focused on the surveillance of the exposure of buffalo milkers in contact with both animals and potentially contaminated equipment, pointing attention on the diffusion of antibiotic- ... ...

Abstract	The research was focused on the surveillance of the exposure of buffalo milkers in contact with both animals and potentially contaminated equipment, pointing attention on the diffusion of antibiotic-resistant
MeSH term(s)	Animals ; Anti-Bacterial Agents/pharmacology ; Buffaloes ; Methicillin Resistance ; Methicillin-Resistant Staphylococcus aureus ; Microbial Sensitivity Tests ; Milk/microbiology ; Oxacillin ; Staphylococcal Infections/epidemiology ; Staphylococcal Infections/microbiology ; Staphylococcal Infections/veterinary ; Staphylococcus ; Staphylococcus aureus
Chemical Substances	Anti-Bacterial Agents ; Oxacillin (UH95VD7V76)
Language	English
Publishing date	2022-04-05
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2175195-X
ISSN	1660-4601 ; 1661-7827
ISSN (online)	1660-4601
ISSN	1661-7827
DOI	10.3390/ijerph19074353
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Article ; Online: Quantitative mapping of keratin networks in 3D.

Windoffer, Reinhard / Schwarz, Nicole / Yoon, Sungjun / Piskova, Teodora / Scholkemper, Michael / Stegmaier, Johannes / Bönsch, Andrea / Di Russo, Jacopo / Leube, Rudolf E

eLife

2022 Volume 11

Abstract: Mechanobiology requires precise quantitative information on processes taking place in specific 3D microenvironments. Connecting the abundance of microscopical, molecular, biochemical, and cell mechanical data with defined topologies has turned out to be ... ...

Abstract	Mechanobiology requires precise quantitative information on processes taking place in specific 3D microenvironments. Connecting the abundance of microscopical, molecular, biochemical, and cell mechanical data with defined topologies has turned out to be extremely difficult. Establishing such structural and functional 3D maps needed for biophysical modeling is a particular challenge for the cytoskeleton, which consists of long and interwoven filamentous polymers coordinating subcellular processes and interactions of cells with their environment. To date, useful tools are available for the segmentation and modeling of actin filaments and microtubules but comprehensive tools for the mapping of intermediate filament organization are still lacking. In this work, we describe a workflow to model and examine the complete 3D arrangement of the keratin intermediate filament cytoskeleton in canine, murine, and human epithelial cells both, in vitro and in vivo. Numerical models are derived from confocal airyscan high-resolution 3D imaging of fluorescence-tagged keratin filaments. They are interrogated and annotated at different length scales using different modes of visualization including immersive virtual reality. In this way, information is provided on network organization at the subcellular level including mesh arrangement, density and isotropic configuration as well as details on filament morphology such as bundling, curvature, and orientation. We show that the comparison of these parameters helps to identify, in quantitative terms, similarities and differences of keratin network organization in epithelial cell types defining subcellular domains, notably basal, apical, lateral, and perinuclear systems. The described approach and the presented data are pivotal for generating mechanobiological models that can be experimentally tested.
MeSH term(s)	Actin Cytoskeleton/metabolism ; Animals ; Cytoskeletal Proteins/metabolism ; Cytoskeleton/metabolism ; Dogs ; Humans ; Intermediate Filaments/metabolism ; Keratins/analysis ; Mice
Chemical Substances	Cytoskeletal Proteins ; Keratins (68238-35-7)
Language	English
Publishing date	2022-02-18
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2687154-3
ISSN	2050-084X ; 2050-084X
ISSN (online)	2050-084X
ISSN	2050-084X
DOI	10.7554/eLife.75894
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Article ; Online: Actuation of Soft Thermoresponsive Hydrogels Mechanically Stimulates Osteogenesis in Human Mesenchymal Stem Cells without Biochemical Factors.

Castro Nava, Arturo / Doolaar, Iris C / Labude-Weber, Norina / Malyaran, Hanna / Babu, Susan / Chandorkar, Yashoda / Di Russo, Jacopo / Neuss, Sabine / De Laporte, Laura

ACS applied materials & interfaces

2023 Volume 16, Issue 1, Page(s) 30–43

Abstract: Mesenchymal stem cells (MSCs) have the potential to differentiate into multiple lineages and can be harvested relatively easily from adults, making them a promising cell source for regenerative therapies. While it is well-known how to consistently ... ...

Abstract	Mesenchymal stem cells (MSCs) have the potential to differentiate into multiple lineages and can be harvested relatively easily from adults, making them a promising cell source for regenerative therapies. While it is well-known how to consistently differentiate MSCs into adipose, chondrogenic, and osteogenic lineages by treatment with biochemical factors, the number of studies exploring how to achieve this with mechanical signals is limited. A relatively unexplored area is the effect of cyclic forces on the MSC differentiation. Recently, our group developed a thermoresponsive
MeSH term(s)	Adult ; Humans ; Osteogenesis/physiology ; Hydrogels/pharmacology ; Hydrogels/metabolism ; Cells, Cultured ; Cell Differentiation/physiology ; Mesenchymal Stem Cells
Chemical Substances	Hydrogels
Language	English
Publishing date	2023-12-27
Publishing country	United States
Document type	Journal Article
ISSN	1944-8252
ISSN (online)	1944-8252
DOI	10.1021/acsami.3c11808
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