Directly after this Editorial (Hall 2021) is the latest instalment of the Biophysical Reviews’ ‘Meet the Editors Series’ (Vassalli 2021). In beginning, this biographical endeavor the journal placed its focus on the five Executive Editors (Olson 2020; Nagayama 2020; Itri 2020; Ho 2020; Jagannathan 2020). After this initial foray, we then started with members of the Editorial Board (Benedetto 2020). This Issue's contribution by Dr. Massimo Vassalli, from the University of Glasgow, is scientifically intriguing. Describing his research progression over a career spanning fields as diverse as theoretical physics and the mechanobiology of cells; it is clear that Dr. Vassalli has both an interesting personal and research story to tell. After reading this piece, one appreciates that the journal is lucky to have him as a member of its Editorial Board (Vassalli 2021). The next article in the front matter section is a Commentary by Prof. Juan-Carmelo Gomez-Fernandez (Gomez-Fernandez 2021). As the Secretary General of IUPAB, Prof. Gomez-Fernandez is one of the key executive members of the organization. In this commentary, he first breaks down how the COVID-19 pandemic has disrupted the activities of IUPAB in 2020, before next describing the planned IUPAB activities for 2021 and beyond (along with their contingencies in case of further disruption).
The first review article (Daria et al. 2021) is concerned with the latest developments in the biophysical design and construction of neural networks. For the reader casually perusing this summary, I point out the atypical aspect of this Review being that these neural networks are not the computational structures associated with machine learning that we so often hear about, but rather the product of actual culturing and machine interfacing of neurons based on opto-genetic/opto-electronic transduction principles. After providing an overview of the biophysics of neurons in isolation and in collection (neuronal circuits), the Review by Daria et al. (2021)discusses the current technical temporal and spatial limitations associated with both, analyzing, and manipulating information transfer in experiments involving individual neurons and neuronal arrays. With much scientific and popular interest in the machine brain interface, this review article provides a digestible introduction to the field along with an excellent presentation of the state-of-the-art and existing open questions.
The second Review deals with the biophysical properties of a particular class of short peptides that exhibit cytotoxic antibacterial properties (Cardoso et al. 2021). Reviewing many demonstrated examples of such peptide-based antibacterial and antifungal activity in nature, the authors speculate how the targeted exploitation of this class of short peptide sequences proffers an avenue for the rational development of new classes of antibiotic and antifungal medicines. Particularly comprehensive in its approach, this article (Cardoso et al. 2021) reviews areas as diverse as models of lipid membrane disruption, the quaternary state dependence of the antimicrobial peptide’s bioactivity, and modern bioinformatics-assisted and experimental combinatorial chemistry-based approaches for enhancing peptide cytotoxicity.
The third review article (Prabakaran et al. 2021) deals with the subject of quantitative modeling of protein aggregation. Due to its causative association with debilitating diseases such as type 2 diabetes and Alzheimer’s, along with the growing recognition of the role it plays as a fundamental regulator ofmany biochemical pathways, research into protein aggregation has proceeded apace over recent years. With the initial recognition of the peptide origin of amyloid (Eanes and Glenner 1968; Glenner et al. 1971; Glenner and Wong 1984), a great deal of research effort has been made to quantitatively describe the structural nature of the protein aggregate and the physical mechanism of its production and regulation, both in vitro, and in the cell (Rochet and Lansbury 2000; Greenwald and Riek 2010; Balchin et al. 2016; Fitzpatrick and Saibil 2019; Hirota et al. 2019). Indeed, different aspects of these topics have been popular subject areas for review within this journal. This Review by Prabakaran et al. (2021) differs from others in the field in that it takes a particularly practical approach by reviewing and benchmarking published methods for predictingif a particular peptide sequence will form an aggregate. One particularly remarkable result to emanate from this benchmarking effort was the authors’ finding that the predictive power of three highly cited (and utilized) methods for estimating amyloid formation propensity from unknown proteins (Chiti et al. 2003; DuBay et al. 2004; Tartaglia et al. 2005) all exhibited correlations in the range [−0.4, 0.4] (i.e., effectively none) when tested against more expansive benchmarked experimental data sets than those on which they were trained and developed (Table 5 (Prabakaran et al. 2021)). Anotherinteresting area covered by this review article involved state-of-the-art approaches for increasing the speed, size, and accuracy (sometimes independently of each other) of molecular dynamics-based simulations.
In a change of direction, the fourth review article of Issue 1 (Poillot et al. 2021) adopts a materials science/solid-state physics perspective to discuss structural deformations of collagen within human cartilage and the capacity of strain-induced deformations of this polymer to induce an electrical potential difference—a phenomenon relating to the piezoelectric effect. In reviewing this area, Poillot et al. (2021) first present the known physicochemical effectors of measured potential difference (and/or current flow) within the fluid/solid environment of cartilage placed under load. Breaking down the contributions associated with fluid flow and charged ion diffusion, the authors review the additional contributing role emanating from structural deformation of the collagen itself. Redistribution of the charged groups within the collagen (when the polymer is stretched) generates different local potential differences both along and perpendicular to the fiber axis with the chance for multiple contributions from many aligned and bundled fibers (with the degree of alignment also changing under load). Results of numerical modelling are presented and reinforced with discussion of experiments based on piezoresponse force microscopy—a modified atomic force microscopy that incorporates an alternating current applied through the cantilever and microscope tip (Poillot et al. 2021).
The fifth review article within this Issue’s collection examines what is known about the structural biology of serotonin receptors (Sarkar et al. 2021). As an important member of the G protein–coupled receptor (GPCR) superfamily, serotonin receptors act as the chief transducer of the brain signaling chemical serotonin (also known as 5-hydroxy tryptamine, 5HT). Through collation and comparison of X-ray and cryoelectron microscopy–generated structures of various ligand-complexed and non-ligand-complexed serotonin receptors (both fragments and complete receptors inclusive of supporting lipid), the authors discuss potential avenues of drug development and comment on the likelihood of various current models of GPCR activity. The arguments made on the basis of structural data are extended through analysis of recent coarse grained molecular dynamics simulations made on serotonin receptors (Sarkar et al. 2021]. As serotonin is one of the chief modifiers of mood, this review article by Sarkar et al. (2021) provides a fascinating molecular insight into the way we think and feel.
The sixth entry, from Sackmann and Tanaka, reviews the fundamental role of the lipid membrane in generating eukaryotic cell polarization and cell migration based on a crawling mechanism (Sackmann and Tanaka 2021). The review begins with an introduction of the two general modes of eukaryotic cell crawling based on either amoeboid movement (pseudopodial projection due to differential weakness in the membrane) or mesenchymal migration (actively driven by bundled actin fiber projection originating from within the cytosol). Focusing on the mesenchymal mode, thesubsequent exposition reviews lipid phase separation driven by the phosphoinositide 3-kinase (PI3K) enzyme–catalyzed conversion of phosphatidylinositol (4,5)-bisphosphate (PIP2) to phosphatidylinositol (3,4,5)-trisphosphate (PIP3). Introducing supporting evidence gained largely from reflection interference contrast microscopy (RICM) measurements, the authors discuss how this key lipid chemical transition results in membrane phase separation, followed by selective peripheral and integral protein localization that ultimately stimulates actin fiber polymerization and differential external protein attachment through stimulation of integrin activity. Introducing the downstream biochemical players in the cellular attachment and release oscillatory cycle, the authors do a very admirable job of making the complex subject of the cell's pulling and pushing events comprehensible, with the underlying physical chemistry not lost in an acronymsalad of pathway components (Sackmann and Tanaka 2021).
The seventh contribution is a short review vignette that discusses the biochemical pathways directing tissue remodeling in varicose vein formation within the leg (Saberianpour et al. 2021). Dealing with the topic of mechanobiology, this review article describes the mechano-transduction principles (based on changes in the activity of integrins, ion channels, and G protein receptors) that translate changes in shear velocity and lateral pressure, occurring within the vein lumen, to cellular growth patterns in the surrounding vasculature.Describing how downstream communication is carried out by changes in the expression of hypoxia inducible factors (HIF) and matrix metallopeptidases (MMP), this Review article discusses how the surrounding extracellular matrix can be modified to produce the varicose phenotype (Saberianpour et al. 2021).
The final Review of Issue 1 is concerned with the topic of biocompatible ionic liquids (Le Donne and Bodo 2021). For those unfamiliar with the topic, the term ionic liquid is typically reserved for a special class of molten salts that are liquid below 100 °C. With the potential to be constructed from a plethora of different highly chemically substituted cations and anions (all relatively loosely held together by ionic bonds), the development of ionic liquids over the last 100 years has presented a novel solvent-based alternative for the rational design of chemical catalysts, with a design philosophy inherently different tosolid-state or enzymatic methodologies. In their article, Le Donne and Bodo (2021) review the development of a particular class of ionic liquids in which the cation chemistry is based on the cholinium ion ((2-hydroxyethyl)trimethylammonium), a chemical component naturally found within the human body. Treating issues relating to the synthesis, biocompatibility, and physical simulation of liquid structure, this article provides a fascinating insight into a potentially non-toxic range of ionic liquids with ‘tunable’ chemical properties.