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Application of Scanning Probe Techniques in the Study of Biomaterials and Biomechanisms

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A special issue of Materials (ISSN 1996-1944). This special issue belongs to the section "Biomaterials".

Deadline for manuscript submissions: closed (10 August 2023) | Viewed by 24367

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Special Issue Editors

Dr. Claudio Canale

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Guest Editor

Department of Physics, University of Genoa, Genoa, Italy
Interests: AFM; biophysics; misfolded protein diseases; mechano-biology

Dr. Ornella Cavalleri

E-Mail Website
Guest Editor

Department of Physics, University of Genoa, Genoa, Italy
Interests: anodic oxides; biomaterials; biofunctionalization; self-assembled monolayers; oligonucleotide films; scanning probe microscopy; spectroscopic ellipsometry; X-ray photoelectron spectroscopy
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Biomaterials are particular substances, generally thought for a medical purpose, specifically designed to interact with biological materials. A fundamental property of biomaterials is bio-compatibility, since they have to adapt and integrate biological materials. One of the strategies followed in the development of biomaterials is bio-inspiration; this means mimicking the natural properties of the biological element to make materials accepted by the body. The idea is to mimic nature not only in terms of chemical, but also physical properties. In particular, mechanical properties play a pivotal role in biomedical applications, and they can span over broad range values, e.g., soft (brain, liver, etc.) or hard (bones, teeth, etc.) tissue.

The characterization of the mechanical properties of a biomaterial and of its biological counterpart is fundamental. Biomechanics is not restricted to the definition of the sample elasticity or stiffness, since other aspects, such as bio-tribology or adhesion properties, are essential.

Scanning probe techniques gained a pivotal role in bio-mechanics, since they provide mechanical characterization, working in a physiological-like environment, spanning on a broad range of elastic moduli (from 10 to 109 Pa), or adhesion/traction forces (10-12 N to 10-7 N).

This Special Issue aims to highlight and discuss the modern trends of scanning probe techniques in biomechanical applications.

It is my pleasure to invite you to submit a manuscript for this Special Issue. Full papers, communications, and reviews are all welcome.

Dr. Claudio Canale
Prof. Ornella Cavalleri
Guest Editors

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Keywords

Scanning probe microscopy
Biomechanics
Biomimetics
Elasticity
Bio-tribology
Cell adhesion
Molecular stability

Published Papers (10 papers)

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Research

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12 pages, 1625 KiB

Open AccessArticle

Biofunctionalization of Porous Titanium Oxide through Amino Acid Coupling for Biomaterial Design

by Paolo Canepa, Danijela Gregurec, Nara Liessi, Silvia Maria Cristina Rotondi, Sergio Enrique Moya, Enrico Millo, Maurizio Canepa and Ornella Cavalleri

Materials 2023, 16(2), 784; https://0-doi-org.brum.beds.ac.uk/10.3390/ma16020784 - 13 Jan 2023

Cited by 3 | Viewed by 1308

Abstract

Porous transition metal oxides are widely studied as biocompatible materials for the development of prosthetic implants. Resurfacing the oxide to improve the antibacterial properties of the material is still an open issue, as infections remain a major cause of implant failure. We investigated the functionalization of porous titanium oxide obtained by anodic oxidation with amino acids (Leucine) as a first step to couple antimicrobial peptides to the oxide surface. We adopted a two-step molecular deposition process as follows: self-assembly of aminophosphonates to titanium oxide followed by covalent coupling of Fmoc-Leucine to aminophosphonates. Molecular deposition was investigated step-by-step by Atomic Force Microscopy (AFM) and X-ray Photoemission Spectroscopy (XPS). Since the inherent high roughness of porous titanium hampers the analysis of molecular orientation on the surface, we resorted to parallel experiments on flat titanium oxide thin films. AFM nanoshaving experiments on aminophosphonates deposited on flat TiO₂ indicate the formation of an aminophosphonate monolayer while angle-resolved XPS analysis gives evidence of the formation of an oriented monolayer exposing the amine groups. The availability of the amine groups at the outer interface of the monolayer was confirmed on both flat and porous substrates by the following successful coupling with Fmoc-Leucine, as indicated by high-resolution XPS analysis. Full article

(This article belongs to the Special Issue Application of Scanning Probe Techniques in the Study of Biomaterials and Biomechanisms)

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16 pages, 5195 KiB

Open AccessArticle

Supervised Learning for Predictive Pore Size Classification of Regenerated Cellulose Membranes Based on Atomic Force Microscopy Measurements

by Alex Hadsell, Huong Chau, Richard Barber, Jr., Unyoung Kim and Maryam Mobed-Miremadi

Materials 2021, 14(21), 6724; https://0-doi-org.brum.beds.ac.uk/10.3390/ma14216724 - 08 Nov 2021

Cited by 1 | Viewed by 1862

Abstract

Nanoporous dialysis membranes made of regenerated cellulose are used as molecular weight cutoff standards in bioseparations. In this study, mesoporous standards with Stokes’ radii (50 kDa/2.7 nm, 100 kDa/3.4 nm and 1000 kDa/7.3 nm) and overlapping skewed distributions were characterized using AFM, with the specific aim of generating pore size classifiers for biomimetic membranes using supervised learning. Gamma transformation was used prior to conducting discriminant analysis in terms of the area under the receiver operating curve (AUC) and classification accuracy (Acc). Monte Carlo simulations were run to generate datasets (n = 10) on which logistic regression was conducted using a constant ratio of 80:20 (measurement:algorithm training), followed by algorithm validation by WEKA. The proposed algorithm can classify the 1000 kDa vs. 100 kDa (AUC > 0.8) correctly, but discrimination is weak for the 100 kDa vs. 50 kDa (AUC < 0.7), the latter being attributed to the instrument accuracy errors below 5 nm. As indicated by the results of the cross-validation study, a test size equivalent to 70% (AUC_tapping = 0.8341 ± 0.0519, Acc_tapping = 76.8% ± 5.9%) and 80% (AUC_fluid = 0.7614 ± 0.0314, Acc_tfluid = 76.2% ± 1.0%) of the training sets for the tapping and fluid modes are needed for correct classification, resulting in predicted reduction of scan times. Full article

(This article belongs to the Special Issue Application of Scanning Probe Techniques in the Study of Biomaterials and Biomechanisms)

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16 pages, 5116 KiB

Open AccessArticle

AFM and Fluorescence Microscopy of Single Cells with Simultaneous Mechanical Stimulation via Electrically Stretchable Substrates

by Natalia Becerra, Barbara Salis, Mariateresa Tedesco, Susana Moreno Flores, Pasquale Vena and Roberto Raiteri

Materials 2021, 14(15), 4131; https://0-doi-org.brum.beds.ac.uk/10.3390/ma14154131 - 24 Jul 2021

Cited by 9 | Viewed by 2532

Abstract

We have developed a novel experimental set-up that simultaneously, (i) applies static and dynamic deformations to adherent cells in culture, (ii) allows the visualization of cells under fluorescence microscopy, and (iii) allows atomic force microscopy nanoindentation measurements of the mechanical properties of the cells. The cell stretcher device relies on a dielectric elastomer film that can be electro-actuated and acts as the cell culture substrate. The shape and position of the electrodes actuating the film can be controlled by design in order to obtain specific deformations across the cell culture chamber. By using optical markers we characterized the strain fields under different electrode configurations and applied potentials. The combined setup, which includes the cell stretcher device, an atomic force microscope, and an inverted optical microscope, can assess in situ and with sub-micron spatial resolution single cell topography and elasticity, as well as ion fluxes, during the application of static deformations. Proof of performance on fibroblasts shows a reproducible increase in the average cell elastic modulus as a response to applied uniaxial stretch of just 4%. Additionally, high resolution topography and elasticity maps on a single fibroblast can be acquired while the cell is deformed, providing evidence of long-term instrumental stability. This study provides a proof-of-concept of a novel platform that allows in situ and real time investigation of single cell mechano-transduction phenomena with sub-cellular spatial resolution. Full article

(This article belongs to the Special Issue Application of Scanning Probe Techniques in the Study of Biomaterials and Biomechanisms)

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16 pages, 4921 KiB

Open AccessArticle

Estrogen Modulates Epithelial Breast Cancer Cell Mechanics and Cell-to-Cell Contacts

by Barbara Zbiral, Andreas Weber, Jagoba Iturri, Maria d. M. Vivanco and José L. Toca-Herrera

Materials 2021, 14(11), 2897; https://0-doi-org.brum.beds.ac.uk/10.3390/ma14112897 - 28 May 2021

Cited by 6 | Viewed by 2457

Abstract

Excessive estrogen exposure is connected with increased risk of breast cancer and has been shown to promote epithelial-mesenchymal-transition. Malignant cancer cells accumulate changes in cell mechanical and biochemical properties, often leading to cell softening. In this work we have employed atomic force microscopy to probe the influence of estrogen on the viscoelastic properties of MCF-7 breast cancer cells cultured either in normal or hormone free-medium. Estrogen led to a significant softening of the cells in all studied cases, while growing cells in hormone free medium led to an increase in the studied elastic and viscoelastic moduli. In addition, fluorescence microscopy shows that E-cadherin distribution is changed in cells when culturing them under estrogenic conditions. Furthermore, cell-cell contacts seemed to be weakened. These results were supported by AFM imaging showing changes in surfaces roughness, cell-cell contacts and cell height as result of estrogen treatment. This study therefore provides further evidence for the role of estrogen signaling in breast cancer. Full article

(This article belongs to the Special Issue Application of Scanning Probe Techniques in the Study of Biomaterials and Biomechanisms)

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12 pages, 1559 KiB

Open AccessArticle

Scaling Concepts in Serpin Polymer Physics

by Samuele Raccosta, Fabio Librizzi, Alistair M. Jagger, Rosina Noto, Vincenzo Martorana, David A. Lomas, James A. Irving and Mauro Manno

Materials 2021, 14(10), 2577; https://0-doi-org.brum.beds.ac.uk/10.3390/ma14102577 - 15 May 2021

Cited by 4 | Viewed by 2920

Abstract

α_{1}

α_{1}

-Antitrypsin is a protease inhibitor belonging to the serpin family. Serpin polymerisation is at the core of a class of genetic conformational diseases called serpinopathies. These polymers are known to be unbranched, flexible, and heterogeneous in size with a beads-on-a-string appearance viewed by negative stain electron microscopy. Here, we use atomic force microscopy and time-lapse dynamic light scattering to measure polymer size and shape for wild-type (M) and Glu342→Lys (Z)

α_{1}

-antitrypsin, the most common variant that leads to severe pathological deficiency. Our data for small polymers deposited onto mica and in solution reveal a power law relation between the polymer size, namely the end-to-end distance or the hydrodynamic radius, and the polymer mass, proportional to the contour length. We use the scaling concepts of polymer physics to assess that

α_{1}

-antitrypsin polymers are random linear chains with a low persistence length. Full article

(This article belongs to the Special Issue Application of Scanning Probe Techniques in the Study of Biomaterials and Biomechanisms)

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15 pages, 3631 KiB

Open AccessArticle

Atomic Force Microscopy Investigation of the Interactions between the MCM Helicase and DNA

by Amna Abdalla Mohammed Khalid, Pietro Parisse, Barbara Medagli, Silvia Onesti and Loredana Casalis

Materials 2021, 14(3), 687; https://0-doi-org.brum.beds.ac.uk/10.3390/ma14030687 - 02 Feb 2021

Cited by 1 | Viewed by 2328

Abstract

The MCM (minichromosome maintenance) protein complex forms an hexameric ring and has a key role in the replication machinery of Eukaryotes and Archaea, where it functions as the replicative helicase opening up the DNA double helix ahead of the polymerases. Here, we present a study of the interaction between DNA and the archaeal MCM complex from Methanothermobacter thermautotrophicus by means of atomic force microscopy (AFM) single molecule imaging. We first optimized the protocol (surface treatment and buffer conditions) to obtain AFM images of surface-equilibrated DNA molecules before and after the interaction with the protein complex. We discriminated between two modes of interaction, one in which the protein induces a sharp bend in the DNA, and one where there is no bending. We found that the presence of the MCM complex also affects the DNA contour length. A possible interpretation of the observed behavior is that in one case the hexameric ring encircles the dsDNA, while in the other the nucleic acid wraps on the outside of the ring, undergoing a change of direction. We confirmed this topographical assignment by testing two mutants, one affecting the N-terminal β-hairpins projecting towards the central channel, and thus preventing DNA loading, the other lacking an external subdomain and thus preventing wrapping. The statistical analysis of the distribution of the protein complexes between the two modes, together with the dissection of the changes of DNA contour length and binding angle upon interaction, for the wild type and the two mutants, is consistent with the hypothesis. We discuss the results in view of the various modes of nucleic acid interactions that have been proposed for both archaeal and eukaryotic MCM complexes. Full article

(This article belongs to the Special Issue Application of Scanning Probe Techniques in the Study of Biomaterials and Biomechanisms)

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12 pages, 1702 KiB

Open AccessArticle

Spatially Resolved Correlation between Stiffness Increase and Actin Aggregation around Nanofibers Internalized in Living Macrophages

by Guoqiao Zhou, Bokai Zhang, Liyu Wei, Han Zhang, Massimiliano Galluzzi and Jiangyu Li

Materials 2020, 13(14), 3235; https://0-doi-org.brum.beds.ac.uk/10.3390/ma13143235 - 21 Jul 2020

Cited by 6 | Viewed by 2289

Abstract

Plasticity and functional diversity of macrophages play an important role in resisting pathogens invasion, tumor progression and tissue repair. At present, nanodrug formulations are becoming increasingly important to induce and control the functional diversity of macrophages. In this framework, the internalization process of nanodrugs is co-regulated by a complex interplay of biochemistry, cell physiology and cell mechanics. From a biophysical perspective, little is known about cellular mechanics’ modulation induced by the nanodrug carrier’s internalization. In this study, we used the polylactic-co-glycolic acid (PLGA)–polyethylene glycol (PEG) nanofibers as a model drug carrier, and we investigated their influence on macrophage mechanics. Interestingly, the nanofibers internalized in macrophages induced a local increase of stiffness detected by atomic force microscopy (AFM) nanomechanical investigation. Confocal laser scanning microscopy revealed a thickening of actin filaments around nanofibers during the internalization process. Following geometry and mechanical properties by AFM, indentation experiments are virtualized in a finite element model simulation. It turned out that it is necessary to include an additional actin wrapping layer around nanofiber in order to achieve similar reaction force of AFM experiments, consistent with confocal observation. The quantitative investigation of actin reconfiguration around internalized nanofibers can be exploited to develop novel strategies for drug delivery. Full article

(This article belongs to the Special Issue Application of Scanning Probe Techniques in the Study of Biomaterials and Biomechanisms)

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15 pages, 2139 KiB

Open AccessArticle

Morphological and Mechanical Characterization of DNA SAMs Combining Nanolithography with AFM and Optical Methods

by Giulia Pinto, Paolo Canepa, Claudio Canale, Maurizio Canepa and Ornella Cavalleri

Materials 2020, 13(13), 2888; https://0-doi-org.brum.beds.ac.uk/10.3390/ma13132888 - 27 Jun 2020

Cited by 10 | Viewed by 2366

Abstract

The morphological and mechanical properties of thiolated ssDNA films self-assembled at different ionic strength on flat gold surfaces have been investigated using Atomic Force Microscopy (AFM). AFM nanoshaving experiments, performed in hard tapping mode, allowed selectively removing molecules from micro-sized regions. To image the shaved areas, in addition to the soft contact mode, we explored the use of the Quantitative Imaging (QI) mode. QI is a less perturbative imaging mode that allows obtaining quantitative information on both sample topography and mechanical properties. AFM analysis showed that DNA SAMs assembled at high ionic strength are thicker and less deformable than films prepared at low ionic strength. In the case of thicker films, the difference between film and substrate Young’s moduli could be assessed from the analysis of QI data. The AFM finding of thicker and denser films was confirmed by X-Ray Photoelectron Spectroscopy (XPS) and Spectroscopic Ellipsometry (SE) analysis. SE data allowed detecting the DNA UV absorption on dense monomolecular films. Moreover, feeding the SE analysis with the thickness data obtained by AFM, we could estimate the refractive index of dense DNA films. Full article

(This article belongs to the Special Issue Application of Scanning Probe Techniques in the Study of Biomaterials and Biomechanisms)

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Review

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22 pages, 4863 KiB

Open AccessReview

Insights in Cell Biomechanics through Atomic Force Microscopy

by Sajedeh Kerdegari, Paolo Canepa, Davide Odino, Reinier Oropesa-Nuñez, Annalisa Relini, Ornella Cavalleri and Claudio Canale

Materials 2023, 16(8), 2980; https://0-doi-org.brum.beds.ac.uk/10.3390/ma16082980 - 09 Apr 2023

Cited by 3 | Viewed by 2190

Abstract

We review the advances obtained by using Atomic Force Microscopy (AFM)-based approaches in the field of cell/tissue mechanics and adhesion, comparing the solutions proposed and critically discussing them. AFM offers a wide range of detectable forces with a high force sensitivity, thus allowing a broad class of biological issues to be addressed. Furthermore, it allows for the accurate control of the probe position during the experiments, providing spatially resolved mechanical maps of the biological samples with subcellular resolution. Nowadays, mechanobiology is recognized as a subject of great relevance in biotechnological and biomedical fields. Focusing on the past decade, we discuss the intriguing issues of cellular mechanosensing, i.e., how cells sense and adapt to their mechanical environment. Next, we examine the relationship between cell mechanical properties and pathological states, focusing on cancer and neurodegenerative diseases. We show how AFM has contributed to the characterization of pathological mechanisms and discuss its role in the development of a new class of diagnostic tools that consider cell mechanics as new tumor biomarkers. Finally, we describe the unique ability of AFM to study cell adhesion, working quantitatively and at the single-cell level. Again, we relate cell adhesion experiments to the study of mechanisms directly or secondarily involved in pathologies. Full article

(This article belongs to the Special Issue Application of Scanning Probe Techniques in the Study of Biomaterials and Biomechanisms)

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12 pages, 2781 KiB

Open AccessReview

AFM Characterization of Halloysite Clay Nanocomposites’ Superficial Properties: Current State-of-the-Art and Perspectives

by Mariafrancesca Cascione, Valeria De Matteis, Francesca Persano and Stefano Leporatti

Materials 2022, 15(10), 3441; https://0-doi-org.brum.beds.ac.uk/10.3390/ma15103441 - 10 May 2022

Cited by 3 | Viewed by 2967

Abstract

Natural halloysite clay nanotubes (HNTs) are versatile inorganic reinforcing materials for creating hybrid composites. Upon doping HNTs with polymers, coating, or loading them with bioactive molecules, the production of novel nanocomposites is possible, having specific features for several applications. To investigate HNTs composites nanostructures, AFM is a very powerful tool since it allows for performing nano-topographic and morpho-mechanical measurements in any environment (air or liquid) without treatment of samples, like electron microscopes require. In this review, we aimed to provide an overview of recent AFM investigations of HNTs and HNT nanocomposites for unveiling hidden characteristics inside them envisaging future perspectives for AFM as a smart device in nanomaterials characterization. Full article

(This article belongs to the Special Issue Application of Scanning Probe Techniques in the Study of Biomaterials and Biomechanisms)

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