Biophysica, Volume 2, Issue 3 (September 2022) – 12 articles

Physical roots, exemplifications and consequences of periodic and aperiodic ordering (represented by Fibonacci series) in biological systems are discussed. The physical and biological roots and role of symmetry and asymmetry appearing in biological patterns are addressed. A generalization of the Curie–Neumann principle as applied to biological objects is presented, briefly summarized as: “asymmetry is what creates a biological phenomenon”. The “top-down” and “bottom-up” approaches to the explanation of symmetry in organisms are presented and discussed in detail. The “top-down” approach implies that the symmetry of the biological structure follows the symmetry of the media in which this structure is functioning; the “bottom-up” approach, in turn, accepts that the symmetry of biological structures emerges from the symmetry of molecules constituting the structure. A diversity of mathematical measures applicable for quantification of order in biological patterns is introduced. The continuous, Shannon and Voronoi measures of symmetry/ordering and their application to biological objects are addressed. The fine structure of the notion of “order” is discussed. Informational/algorithmic roots of order inherent in the biological systems are considered. Ordered/symmetrical patterns provide an economy of biological information, necessary for the algorithmic description of a biological entity. The application of the Landauer principle bridging physics and theory of information to the biological systems is discussed. Full article

We propose a model for bacterial Quorum Sensing based on an auxiliary electrostatic-like interaction originating from a fictitious electrical charge that represents bacteria activity. A cooperative mechanism for charge/activity exchange is introduced to implement chemotaxis and replication. The bacteria system is thus represented by means of a complex resistor network where link resistances take into account the allowed activity-flow among individuals. By explicit spatial stochastic simulations, we show that the model exhibits different quasi-realistic behaviors from colony formation to biofilm aggregation. The electrical signal associated with Quorum Sensing is analyzed in space and time and provides useful information about the colony dynamics. In particular, we analyze the transition between the planktonic and colony phases as the intensity of Quorum Sensing is varied. Full article

The ability of dying cancer cells to induce an anticancer immune response can increase the effectiveness of anticancer therapies, and such type of death is termed immunogenic cell death (ICD). Cells can die along the ICD pathway when exposed not only to chemo- and immunotherapeutics, but also to various types of radiation, such as ionizing radiation and cold atmospheric plasma jets (CAP). We have previously shown that CAP, lactaptin, and a recombinant vaccinia virus encoding lactaptin induce in vitro molecular changes typical of ICD in cancer cells. In the current work, we treated MX-7 rhabdomyosarcoma cells with CAP and lactaptin-based anticancer drugs and evaluated the immunological effects of the treated cells. We showed that dendritic cells (DCs) captured cells treated with various ICD inducers with different efficiency. CAP-treated cells were weakly potent in inducing the maturation of DCs according to MHC II externalization. Moreover, CAP-treated cells were worse in the stimulation of IFN-α release in vitro and were poorly captured by spleen DCs in vivo. Under the irradiation conditions used, CAP was not capable of activating a significant immunological anti-tumor effect in vivo. It is possible that modifications of the CAP irradiation regimen will enhance the activation of the immune system. Full article

Two groups of Cistus creticus seedlings were grown in two chambers under controlled environmental conditions. In one of the chambers, a continuously emitting base unit of a wireless telephone was placed. After fifty days of culture, the two groups of plants were removed and thoroughly investigated and compared. The aboveground parts of the exposed plants were retarded in development while their roots exhibited increased biomass, compared to the controls. There was a minor decrease in the absorbance of the photosynthetic pigments in exposed plants, while an overproduction of Reactive Oxygen Species (ROS) ROS in their leaves and roots was detected. The expression of the L-Dopa decarboxylase (DDC) seemed to “erupt” following the exposure to radiation in both shoots and roots of the stressed plants, and their roots slow down their secondary development; strangely, the phenolic content is reduced in their leaves, the external topography of which indicates a rather xeromorphic response. We may suggest that Cistus creticus plants, forced by the radiation stress, can finely tune their metabolic pathways in a way that can be useful in the pharmaceutical industry. Full article

The amount of water-accessible-surface-area, WASA, buried upon protein–protein association is a good measure of the non-covalent complex stability in water; however, the dependence of the binding Gibbs free energy change upon buried WASA proves to be not trivial. We assign a precise physicochemical role to buried WASA in the thermodynamics of non-covalent association and perform close scrutiny of the contributions favoring and those contrasting protein–protein association. The analysis indicates that the decrease in solvent-excluded volume, an entropic effect, described by means of buried WASA, is the molecular driving force of non-covalent association in water. Full article

The catalytic mechanism of hammerhead ribozymes (HHRzs) attracted great attention in relation to the chemical origin of life. However, the basicity (pK_a) of the catalytic sites of HHRzs has not been studied so far. As a result, the investigation of the currently assumed mechanism from an experimentally derived pK_a value has been impossible. In HHRzs, there exists a highly functionalized structural unit (A9-G10.1 site) with a catalytic residue (G12) for the nucleophile activation and metal ion-binding residue (G10.1). As inferred from this fact, there might be a possibility that HHRzs may utilize specific functions of the A9-G10.1 motif for the catalytic reaction. Therefore, here we studied the basicity of G12/G10.1-corresponding residues using RNA duplexes including the A9-G10.1 motif without other conserved residues of HHRzs. From the pH-titration experiments with NMR spectra, we have obtained the intrinsic basicity of the G12/G10.1-corresponding residues in the motif, with pK_a > 11.5 (N1 of G12) and pK_a 4.5 (N7 of G10.1) for the first time. Based on the derived irregular basicity, their correlation with a catalytic activity and a metal affinity were investigated. In total, the derived thermodynamic properties are an intrinsic nature of the exclusive catalytic unit of HHRzs, which will be an outstanding pivot point for the mechanistic analyses. Full article

As 90% of cancer-patient deaths are due to metastasis, novel therapeutics that selectively target and kill metastatic cells are desperately needed. Matrix metalloproteinase-14 (MMP-14), which plays a critical role in digesting the basement membrane and in inducing cancer cell migration, has been found to be expressed at the cell surface of circulating and metastasized tumor cells in various human cancers. We have recently shown that the IVS4 peptide, which mimics the minimal binding motif of the hemopexin-like (PEX) domain of MMP-14, interrupts MMP-14 dimerization and decreases MMP-14-mediated cell invasion. In this study, cancer-homing nanocarriers were assembled by linking IVS4 to polysaccharide-based nanoparticles (NPs), followed by the encapsulation of a pharmaceutical agent. IVS4-NPs efficiently prevented MMP-14-mediated cell migration and conferred an uptake advantage compared to the control peptide in an MMP-14-dependent manner. While the IVS4-NPs alone were not cytotoxic, drug-encapsulated NPs were shown to effectively target MMP-14-expressing cancer cells. This novel nanotherapeutic is capable of inhibiting MMP-14-mediated functions and efficiently killing MMP-14-expressing cancer cells, without affecting the viability of non-cancer cells. Full article

Shikimate kinase (SK) enzyme is a suitable target for antimicrobial drugs as it is present in pathogenic microorganisms and absent in mammals. A complete understanding of the functioning of this enzyme can unveil novel methods to inactivate it. To do this, a clear understanding of SK performance is needed. Previously, the chemical step of SK was studied in detail, but a study of longer-term scale simulations is still missing. In the present work, we performed molecular dynamics (MD) simulations in the μs time scale that allowed us to explore further regions of the SK energy landscape than previously. Simulations were conducted on the wild-type (WT) enzyme and the R116A and R116K mutants. We analyzed the dynamics of the enzymes through standard MD tools, and we found that the global motions in the mutants were perturbed. These motions can be linked to the observed undetectable binding affinity of the WT enzyme and the R116A and R116K mutants. Full article

Living organisms react to external stimuli to adapt their activity to the environment for survival. Acquired information is encoded by neurons by action potentials (APs) in a series of discrete electrical events. Rapid initiation of the AP is critical for fast reactions and strongly relies on voltage-activated Na⁺-selective channels (NaVs), which are widely expressed by both invertebrate and vertebrate neurons. Intuitively, NaVs of higher mammals should be activated faster than those of any other species. In addition to improved NaV channel structure, central mammalian neurons also demonstrate a patterned distribution of specific types of NaV1 channels at and near the site of AP initiation within the axonal initial segment (AIS). The AIS has different types of fast Nav1 channels and is thought to provide the biological basis for efficient frequency coding of information. In the present work, we review data related to the channels underlying fast initiation of action potentials in vertebrates and invertebrates, along with their evolution, distribution, and known specific roles. Current research has established that all mammalian NaV1 (1.1–1.9) channels share a similar structure, with 4 conservative transmembrane D-domains with a highly homologous sequence, but significant differences in the length of the functional cytoplasmic linkers. Similarly, the structure of NaV1 channels in invertebrates is generally similar to that of mammals, but it shows high variability across the evolutionary tree in the length of the linkers. AP initiation in mammalian cortical neurons is mediated by NaV1.2 and NaV1.6 channels, whereas interneurons mostly rely on NaV1.1 channels in their firing. Although invertebrate NaV1 channels normally display relatively slow kinetics, their activation is fast enough to produce APs, even in simple animals such as Placozoa. Remarkably, fast sodium-based excitability is not limited to animals. Recently, a photosynthetic prokaryote has been found to show rapidly activated sodium currents provided by their independently evolved single D-domain EuKatB sodium channels. Full article

From yeast to mammalian cells, ubiquitination is one of the most conserved, and reversible, eukaryotic post-translational modifications (PTMs) responsible for controlling nearly all cellular processes. Potentially, every single eukaryotic cell can accomplish different ubiquitination processes at once, which in turn control the execution of specific cellular events in time and space with different biological significance (e.g., protein degradation or protein–protein interaction). Overall, all these signals are highly dynamic and need to be finely integrated to achieve a proper cellular response. Altogether, ubiquitination appears to be an extremely complex process, likely more than any other PTMs. Until a few years ago, the prevailing experimental approaches to investigate the different aspects of the ubiquitin system entailed genetic and biochemical analysis. However, recently, reagents and technologies have been developed enabling microscopy-based imaging of ubiquitination to enter the scene. In this paper, we discuss the progress made with conventional (confocal fluorescence microscopy) and non-conventional non-linear microscopy (Atomic Force Microscopy—AFM, Coherent Anti-Stokes Raman Scattering—CARS, Stimulated Raman Scattering—SRS) and we speculate on future developments. Full article

Previous studies have shown that sub-lethal exposure of blue light caused increased bacterial cell membrane permeability. We hypothesized that combining blue light exposure with other antibacterial agents may increase their efficacy. The aim of the present study was to test the combined effect of blue light and sodium fluoride against dental caries pathogen Streptococcus mutans. Sm biofilms were exposed to blue light (400–500 nm) with or without sodium fluoride. Exposed and non-exposed samples were studied for acid production (lactate assay kit), acid tolerance (ATPase assay kit) and bacterial cell membrane damage (fluorescence microscopy). Results showed that the combined treatment significantly reduced the virulence of Sm concomitant with an increase in bacterial cell membrane permeability. Taken together, these results suggest that adjacent blue light exposure may increase fluoride caries preventive properties. Full article

The synthesis of tailored and highly engineered multifunctional pharmaceutical nanocarriers is an emerging field of study in drug delivery applications. They have a high surface-area-to-volume ratio, aiding the targeted drug’s biodistribution and pharmacokinetic properties. Therefore, the characterization of nanocarriers is critical for understanding their physicochemical properties, which significantly impact their molecular and systemic functioning. To achieve specific goals, particle size, surface characteristics, and drug release properties of nanocarriers must be managed. This mini review provides an overview of the applications of non-destructive testing techniques (NDTT) to reveal the characteristics of nanocarriers, considering their surface charge, porosity, size, morphology, and crystalline organization. The compositional and microstructural characterization of nanocarriers through NDTT, such as dynamic light scattering, X-ray diffraction, confocal laser scanning microscopy, ultraviolet-visible spectroscopy, scanning electron microscopy, atomic force microscopy, and nuclear magnetic resonance spectroscopy, have been comprehensively reviewed. Furthermore, NDTT is only used to characterize physicochemical parameters related to the physiological performance of nanocarriers but does not account for nanocarrier toxicity. Hence, it is highly recommended that in the future, NDTT be developed to assess the toxicity of nanocarriers. In addition, by developing more advanced, effective, and precise techniques, such as machine vision techniques using artificial intelligence, the future of using NDTT for nanocarrier characterization will improve the evaluation of internal quality parameters. Full article