Biophysica

21 pages, 1797 KiB

Open AccessArticle

Benefits of Combined Fluorescence Lifetime Imaging Microscopy and Fluorescence Correlation Spectroscopy for Biomedical Studies Demonstrated by Using a Liposome Model System

by Kristina Bruun, Hans-Gerd Löhmannsröben and Carsten Hille

Biophysica 2024, 4(2), 207-227; https://doi.org/10.3390/biophysica4020015 (registering DOI) - 25 Apr 2024

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Abstract

Drug delivery systems play a pivotal role in targeted pharmaceutical transport and controlled release at specific sites. Liposomes, commonly used as drug carriers, constitute a fundamental part of these systems. Moreover, the drug–liposome model serves as a robust platform for investigating interaction processes [...] Read more.

Drug delivery systems play a pivotal role in targeted pharmaceutical transport and controlled release at specific sites. Liposomes, commonly used as drug carriers, constitute a fundamental part of these systems. Moreover, the drug–liposome model serves as a robust platform for investigating interaction processes at both cellular and molecular levels. To advance our understanding of drug carrier uptake mechanisms, we employed fluorescence lifetime imaging microscopy (FLIM) and fluorescence correlation spectroscopy (FCS), leveraging the unique benefits of two-photon (2P) excitation. Our approach utilized giant unilamellar vesicles (GUVs) as a simplified model system for cell membranes, labelled with the amphiphilic fluorescent dye 3,3′-dioctadecyloxa-carbocyanine (DiOC₁₈(3)). Additionally, large unilamellar vesicles (LUVs) functioned as a drug carrier system, incorporating the spectrally distinct fluorescent sulforhodamine 101 (SRh101) as a surrogate drug. The investigation emphasized the diverse interactions between GUVs and LUVs based on the charged lipids employed. We examined the exchange kinetics and structural alterations of liposome carriers during the uptake process. Our study underscores the significance of employing 2P excitation in conjunction with FLIM and FCS. This powerful combination offers a valuable methodological approach for studying liposome interactions, positioning them as an exceptionally versatile model system with a distinct technical advantage. Full article

12 pages, 707 KiB

Open AccessOpinion

Biophysical Breakthroughs Projected for the Phage Therapy of Bacterial Disease

by James P. Chambers, Miranda Aldis, Julie A. Thomas, Cara B. Gonzales, Richard Allen White III and Philip Serwer

Biophysica 2024, 4(2), 195-206; https://doi.org/10.3390/biophysica4020014 - 12 Apr 2024

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Abstract

Past anti-bacterial use of bacteriophages (phage therapy) is already well reviewed as a potential therapeutic response to the emergence of multidrug-resistant, pathogenic bacteria. Phage therapy has been limited by the following. (1) The success rate is too low for routine use and Food [...] Read more.

Past anti-bacterial use of bacteriophages (phage therapy) is already well reviewed as a potential therapeutic response to the emergence of multidrug-resistant, pathogenic bacteria. Phage therapy has been limited by the following. (1) The success rate is too low for routine use and Food and Drug Administration (FDA) approval. (2) Current strategies of routine phage characterization do not sufficiently improve the success rate of phage therapy. (3) The stability of many phages at ambient temperature is not high enough to routinely store and transport phages at ambient temperature. In the present communication, we present new and previous data that we interpret as introductory to biophysically and efficiently transforming phage therapy to the needed level of effectiveness. Included are (1) procedure and preliminary data for the use of native gel electrophoresis (a low-cost procedure) for projecting the therapy effectiveness of a newly isolated phage, (2) data that suggest a way to achieve stabilizing of dried, ambient-temperature phages via polymer embedding, and (3) data that suggest means to increase the blood persistence, and therefore the therapy effectiveness, of what would otherwise be a relatively low-persistence phage. Full article

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13 pages, 3453 KiB

Open AccessArticle

Deciphering the Molecular Interaction Process of Gallium Maltolate on SARS-CoV-2 Main and Papain-Like Proteases: A Theoretical Study

by Kevin Taype-Huanca, Manuel I. Osorio, Diego Inostroza, Luis Leyva-Parra, Lina Ruíz, Ana Valderrama-Negrón, Jesús Alvarado-Huayhuaz, Osvaldo Yañez and William Tiznado

Biophysica 2024, 4(2), 182-194; https://doi.org/10.3390/biophysica4020013 - 10 Apr 2024

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Abstract

This study explored the inhibitory potential of gallium maltolate against severe acute respiratory syndrome coronavirus 2 and main and papain-like proteases. Computational methods, including density functional theory and molecular docking, were used to assess gallium maltolate reactivity and binding interactions. Density functional theory [...] Read more.

This study explored the inhibitory potential of gallium maltolate against severe acute respiratory syndrome coronavirus 2 and main and papain-like proteases. Computational methods, including density functional theory and molecular docking, were used to assess gallium maltolate reactivity and binding interactions. Density functional theory calculations revealed gallium maltolate’s high electron-capturing capacity, particularly around the gallium metal atom, which may contribute to their activity. Molecular docking demonstrated that gallium maltolate can form strong hydrogen bonds with key amino acid residues like glutamate-166 and cysteine-145, tightly binding to main and papain-like proteases. The binding energy and interactions of gallium maltolate were comparable to known SARS-CoV-2 inhibitors like N-[(5-methyl-1,2-oxazol-3-yl)carbonyl]-L-alanyl-L-valyl-N-{(2S,3E)-5-(benzyloxy)-5-oxo-1-[(3S)-2-oxopyrrolidin-3-yl]pent-3-en-2-yl}-L-leucinamide, indicating its potential as an antiviral agent. However, further experimental validation is required to confirm its effectiveness in inhibiting SARS-CoV-2 replication and treating COVID-19. Full article

(This article belongs to the Special Issue The Structure and Function of Proteins, Lipids, and Nucleic Acids)

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14 pages, 558 KiB

Open AccessArticle

Search for Entanglement between Spatially Separated Living Systems: Experiment Design, Results, and Lessons Learned

by Chris Fields, Lorenzo Cohen, Andrew Cusimano, Sharmistha Chakraborty, Phuong Nguyen, Defeng Deng, Shafaqmuhammad Iqbal, Monica Nelson, Daoyan Wei, Arnaud Delorme and Peiying Yang

Biophysica 2024, 4(2), 168-181; https://doi.org/10.3390/biophysica4020012 - 30 Mar 2024

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Abstract

Statistically significant violations of the Clauser–Horne–Shimony–Holt (CHSH) inequality are the “gold standard” test for quantum entanglement between spatially separated systems. Here, we report an experimental design that implements a CHSH test between bioelectric state variables for a human subject and bioelectric and/or biochemical [...] Read more.

Statistically significant violations of the Clauser–Horne–Shimony–Holt (CHSH) inequality are the “gold standard” test for quantum entanglement between spatially separated systems. Here, we report an experimental design that implements a CHSH test between bioelectric state variables for a human subject and bioelectric and/or biochemical state variables for cultured human cells in vitro. While we were unable to obtain evidence for entanglement with this design, observing only classical correlation, we report lessons learned and suggest possible avenues for future studies. Full article

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10 pages, 869 KiB

Open AccessPerspective

Never Fold to Fold Continuously: A Conundrum in Ubiquitin–Proteasome System (UPS)-Mediated Protein Quality Control (PQC)

by Stefano Magnati and Enrico Bracco

Biophysica 2024, 4(2), 158-167; https://doi.org/10.3390/biophysica4020011 - 30 Mar 2024

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Abstract

In the last few decades, the traditional paradigm of teleonomy, in which the amino acid sequence of a protein is tightly associated with its structure and, in turn, with its function, has been partially undermined. The idea of a protein as a two-state [...] Read more.

In the last few decades, the traditional paradigm of teleonomy, in which the amino acid sequence of a protein is tightly associated with its structure and, in turn, with its function, has been partially undermined. The idea of a protein as a two-state object has been superseded by that of understanding it as a multistate object. Indeed, some proteins, or portions of a protein, display intrinsically disordered regions (IDRs), which means that they lack stable secondary or tertiary structures. While we are aware that IDRs are present in almost half of the total human proteins, we are still quite far away from understanding their contextual-specific functions and figuring out how they mechanistically work. In the present perspective article, we will attempt to summarize the role/s of IDRs in ubiquitin–proteasome system (UPS)-mediated protein quality control (PQC) at different levels, ranging from ubiquitination to protein degradation through the proteasome machinery up to their role in decoding the complex ubiquitin code. Ultimately, we will critically discuss the future challenges we are facing to gain insights into the role of IDRs in regulating UPS-mediated PQC. Full article

(This article belongs to the Special Issue Protein Disorder)

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16 pages, 3618 KiB

Open AccessReview

Axial Tomography in Live Cell Microscopy

by Herbert Schneckenburger and Christoph Cremer

Biophysica 2024, 4(2), 142-157; https://doi.org/10.3390/biophysica4020010 - 29 Mar 2024

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Abstract

For many biomedical applications, laser-assisted methods are essential to enhance the three-dimensional (3D) resolution of a light microscope. In this report, we review possibilities to improve the 3D imaging potential by axial tomography. This method allows us to rotate the object in a [...] Read more.

For many biomedical applications, laser-assisted methods are essential to enhance the three-dimensional (3D) resolution of a light microscope. In this report, we review possibilities to improve the 3D imaging potential by axial tomography. This method allows us to rotate the object in a microscope into the best perspective required for imaging. Furthermore, images recorded under variable angles can be combined to one image with isotropic resolution. After a brief review of the technical state of the art, we show some biomedical applications, and discuss future perspectives for Deep View Microscopy and Molecular Imaging. Full article

(This article belongs to the Special Issue Biomedical Optics 2.0)

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14 pages, 2140 KiB

Open AccessReview

Assessing the Impact of Agents with Antiviral Activities on Transmembrane Ionic Currents: Exploring Possible Unintended Actions

by Geng-Bai Lin, Chia-Lung Shih, Rasa Liutkevičienė, Vita Rovite, Edmund Cheung So, Chao-Liang Wu and Sheng-Nan Wu

Biophysica 2024, 4(2), 128-141; https://doi.org/10.3390/biophysica4020009 - 27 Mar 2024

Viewed by 412

Abstract

As the need for effective antiviral treatment intensifies, such as with the coronavirus disease 19 (COVID-19) infection, it is crucial to understand that while the mechanisms of action of these drugs or compounds seem apparent, they might also interact with unexplored targets, such [...] Read more.

As the need for effective antiviral treatment intensifies, such as with the coronavirus disease 19 (COVID-19) infection, it is crucial to understand that while the mechanisms of action of these drugs or compounds seem apparent, they might also interact with unexplored targets, such as cell membrane ion channels in diverse cell types. In this review paper, we demonstrate that many different drugs or compounds, in addition to their known interference with viral infections, may also directly influence various types of ionic currents on the surface membrane of the host cell. These agents include artemisinin, cannabidiol, memantine, mitoxantrone, molnupiravir, remdesivir, SM-102, and sorafenib. If achievable at low concentrations, these regulatory effects on ion channels are highly likely to synergize with the identified initial mechanisms of viral replication interference. Additionally, the immediate regulatory impact of these agents on the ion-channel function may potentially result in unintended adverse effects, including changes in cardiac electrical activity and the prolongation of the QTc interval. Therefore, it is essential for patients receiving these related agents to exercise additional caution to prevent unnecessary complications. Full article

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Biophysica, Volume 4, Issue 2 (June 2024) – 7 articles

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