Biophysical reviews最新文献

The population of cells that make up a tumor, and of their biomolecular conformational ensembles, are heterogeneous at all levels, genetic, epigenetic, and phenotypic. At the cellular level, tumor heterogeneity was described as the "Rosetta Stone of therapy resistance." At the genetic level, tumors consist of divergent tumor (sub)clones. At the phenotypic level, their observed function, clinical attributes, and response to drugs vary. We suggest that the behavior and properties of populations of cells-and of populations of conformational states-are intrinsically connected. This is important. Considering the tumor's disruption of normal cellular processes clarifies why it is crucial to understand the ins and outs of its mechanistic molecular foundation. In reality, the propensities of the tumor's conformational states underly the proliferative potential of its cell populations. These propensities are determined by expression levels, driver mutations, and the tumor cells environment, collectively transforming tumor cells behavior and crucially, drug resistance. We suggest that propensities of the conformations, across the tumor space and over time, shape tumor heterogeneity, and cell plasticity. The conformational states that are preferentially visited can be viewed as phenotypic determinants, and their mutations and altered expression work by allosterically shifting the relative propensities, thus the cell phenotype. Physics (and chemistry) inspire the notion that living things must conform to fundamental laws of science, like dynamic landscapes. Dynamic conformational propensities are at the core of cell life, including tumor cells; their heterogeneity is the formidable, unmet drug resistance challenge.

Structural biology techniques that utilize X-rays have contributed in fundamental ways to our understanding of biological macromolecules, such as proteins and nucleic acids. In addition to static structures, recent advances now allow for the observation of molecular motions using X-rays, facilitated by the many technological developments in both sources and detectors. Leveraging these advances, new approaches have been demonstrated that capture structural dynamics, sometimes with very high spatial resolution. Among the most promising are time-resolved studies, which involve triggering a reaction and capturing snapshots of reaction progression at set time delays. This review focuses on one type of time-resolved experiments, mixing experiments, in which reactants are combined within microfluidic mixers to initiate a reaction. Microfluidic mixers are extremely versatile; different designs can be optimized for various reaction types and compatibility with different structural biology techniques. When compared to other time-resolved approaches, mixing experiments are suitable for the widest range of biological applications. This review provides an overview of the current state of the field, including a review of different mixer types, and offers practical considerations for designing and performing time-resolved mixing studies with various X-ray-based structural biology methods.

Antibiotic resistance presents a significant global concern, worsened by overuse and limited development of new antibiotics. Medical implants, in particular, are increasingly susceptible to bacterial infections. To prevent biofilm formation on implants, it is essential to design specialized surface characteristics that either kill bacteria or inhibit their growth. Nanostructures resembling those found in nature, such as cicada wings, exhibit pronounced antibacterial efficacy. Drawing inspiration from these natural surfaces, artificial nanostructures made with similar features have demonstrated bactericidal effect. The bactericidal mechanism in nanostructures may seem simple, as the nanofeatures pierce through bacterial cells, leading to their death. However, research has shown that it is more complex and requires thorough investigation. Several studies indicate that while the bactericidal mechanism is initiated by mechanical contact, the precise killing process remains uncertain. Numerous experimental and theoretical investigations have aimed to elucidate the exact killing mechanism, yielding diverse conclusions and hypotheses, including cell death attributed to creep failure, motion-induced shear failure, apoptosis-induced programmed cell death and autolytic cell death, among others. This study undertakes a comprehensive review of all proposed death mechanisms. Moreover, it draws conclusions on the killing mechanism by meticulously analyzing the properties of bacterial membranes, their mechanosensing and adhesion mechanisms, energy-based models for bacterial adhesion, and experimental outcomes regarding the bactericidal efficacy of surfaces exhibiting diverse geometries.

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Microneedles (MN) technology has emerged as a transformative tool within the biomedical field, offering innovative solutions to challenges in drug delivery, diagnostics, and therapeutic applications. This review article provides an in-depth exploration of the diverse perspectives and applications of MNs, shedding light on their pivotal role in shaping the future of biomedical research and clinical practice. It begins by elucidating the fundamental principles of MNs: design, fabrication techniques, and materials, highlighting their capacity for minimally invasive access to the skin and underlying tissues. These attributes have driven advancements in transdermal drug delivery, facilitating precise and controlled administration of therapeutics, vaccines, and biologics, thus improving patient compliance and treatment outcomes. Furthermore, this review investigates the growing range of applications for MNs, including biomarker extraction, interstitial fluid (ISF) analysis, and continuous glucose monitoring. MNs enable real-time and minimally invasive monitoring of biochemical markers and have the potential to revolutionize disease diagnostics, personalized medicine, and wellness monitoring. Their compatibility with microfluidic systems further enhances their potential for point-of-care testing. This review serves as a comprehensive guide, highlighting the breadth of opportunities and challenges in leveraging MNs to improve healthcare outcomes and emphasizing the need for continued research and development in this dynamic field.

This Editorial for Volume 17 Issue 2 of Biophysical Reviews introduces the contents of the second Special Issue on the Latin American Federation of Biophysical Societies (LAFeBS). Biophysical Reviews is the official journal of the International Union for Pure and Applied Biophysics (IUPAB). The multidisciplinary scope of the articles in this issue reflects LAFeBS's commitment to highlighting regional contributions to the advancement of biophysics across all its branches.

It has been more than a century since the protamines were found. Protamine continues to exist as a nucleo-protamine complex, similar to how the histone does. In sperm cells of vertebrates, protamine binds to DNA to produce compact chromatin. A more densely packed chromatin is produced when protamines replace histones. It is known that protamine is found in the DNA; however, its precise position inside DNA is not clearly known. Protamine may be bound to DNA in the major groove, according to some studies, while others contend that it is located in the minor groove. Also unknown is the precise physics underlying how protamines force histones out of sperm cells. In this work, an integrated view of the nucleo-protein complex formation regarding protamine's binding location in DNA and the phenomena associated with protamine's binding to DNA which is initiated with the eviction of the histones from the coiled chromatin is presented.

Free energy is a critical parameter in understanding the equilibrium in chemical reactions. It enables us to determine the equilibrium proportion between the different species in the reaction and to predict in which direction the reaction will proceed if a change is performed in the system. Historically, to calculate this value, bulk experiments were performed where a parameter was altered at a gradual rate to change the population until a new equilibrium was established. In protein folding studies, it is common to vary the temperature or chaotropic agents in order to change the population and then to extrapolate to physiological conditions. Such experiments were time-consuming due to the necessity of ensuring equilibrium and reversibility. Techniques of single-molecule manipulation, such as optical/magnetic tweezers and atomic force microscopy, permit the direct measurement of the work performed by a protein undergoing unfolding/refolding at particular forces. Also, with the development of non-equilibrium free energy theorems (Jarzynski equality, Crooks fluctuation theorem, Bennett acceptance ratio, and overlapping method), it is possible to obtain free energy values in experiments far from equilibrium. This review compares different methodologies and their application in optical tweezers. Interestingly, in many proteins, discrepancies in free energy values obtained through different methods suggest additional complexities in the folding pathway, possibly involving intermediate states such as the molten globule. Further studies are needed to confirm their presence and significance.

Supplementary information: The online version contains supplementary material available at 10.1007/s12551-025-01310-0.

The application of membrane-active antimicrobial peptides (AMPs) is considered to be a viable alternative to conventional antibiotics for treating infections caused by multidrug-resistant pathogenic microorganisms. In vitro and in silico biophysical approaches are indispensable for understanding the underlying molecular mechanisms of membrane-active AMPs. Lipid bilayer models are widely used to mimic and study the implication of various factors affecting these bio-active molecules, and their relationship with the physical parameters of the different membranes themselves. The quality and resemblance of these models to their target is crucial for elucidating how these AMPs work. Unfortunately, over the last few decades, no notable efforts have been made to improve or refine membrane mimetics, as it pertains to the elucidation of AMPs molecular mechanisms. In this review, we discuss the importance of improving the quality and resemblance of target membrane models, in terms of lipid composition and distribution, which ultimately directly influence physical parameters such as charge, fluidity, and thickness. In conjunction, membrane and peptide properties determine the global effect of selectivity, activity, and potency. It is therefore essential to define these interactions, and to do so, more refined lipid models are necessary. In this review, we focus on the significant advancements in promoting biomimetic membranes that closely resemble native ones, for which thorough biophysical characterization is key. This includes utilizing more complex lipid compositions that mimic various cell types. Additionally, we discuss important considerations to be taken into account when working with more complex systems.

Understanding the emergence or loss of enzyme functions comprises several approaches, such as genetic, structural, and kinetic studies. Promiscuous enzyme activities have been proposed as starting points for the emergence of novel enzyme functions, for example, through genetic models such as neofunctionalization and subfunctionalization. In both cases, neutral evolution would fix gene redundancy, critical in relaxing functional constraints and allowing specific mutations to drive innovation. The evolution of enzyme activities has a structural basis, with genetic mutations modifying the active site architecture, conformational dynamics, or interaction networks, which leads to the creation, enhancement, or restriction of enzyme functions where epistatic interactions are crucial. These structural changes impact the described kinetic mechanisms like ground-state stabilization (affinity), transition-state stabilization (catalysis), or a combination of both. Case studies across diverse enzyme families illustrate these principles, emphasizing the interplay between genetic, structural, and kinetic approaches. Finally, we discuss the importance of understanding evolutionary mechanisms and their impact on protein engineering and drug design for biomedical and industrial applications. However, these studies highlight that further experimental evolutionary data collection is necessary to enable the training of advanced machine learning models for use in biotechnological applications.

In this report, I describe some of the subjects and problems that we have addressed over the last 25 years in the area of cell signaling using the tools of biological physics. The report covers part of our work on intracellular Ca $_{}^{2+}$ signals, pattern formation, transport of messengers in the interior of cells, quantification of biophysical parameters from experiments, and information transmission. The description includes both our modeling and experimental work highlighting how the tools of physics can give useful insights into the workings of biological systems.