Biophysical reviews最新文献

This editorial introduces the contents of Volume 16, Issue 6 of Biophysical Reviews, the official journal of the International Union for Pure and Applied Biophysics (IUPAB). Highlights of the Issue include an invited review article by David Alsteens, the winner of the 2024 Michèle Auger Award for Young Scientists' Independent Research and a Special Issue Focus involving a series of articles based on topics addressed at the 7th Nanoengineering for Mechanobiology Symposium 2024. The broad scope of articles and the geographically widespread locations of the contributing authors of these and other reviews in the Issue mirror the goals of IUPAB, namely to organize worldwide advancements, co-operation, communication, and education in biophysics.

Atomic force microscopy (AFM) has emerged as a powerful tool for studying biological interactions at the single-molecule level, offering unparalleled insights into receptor-ligand dynamics on living cells. This review discusses key developments in the application of AFM, highlighting its ability to capture nanomechanical properties of cellular surfaces and probe dynamic interactions, such as virus-host binding. AFM's versatility in measuring mechanical forces and mapping molecular interactions in near-physiological conditions is explored. The review also emphasizes how AFM provides critical insights into cell surface organization, receptor functionality, and viral entry mechanisms, advancing the understanding of cellular and molecular processes.

Mechanosensitivity is the ability of cells to sense and respond to mechanical stimuli. In order to do this, cells are endowed with different components that allow them to react to a broad range of stimuli, such as compression or shear forces, pressure, and vibrations. This sensing process, mechanosensing, is involved in fundamental physiological mechanisms, such as stem cell differentiation and migration, but it is also central to the development of pathogenic states. Here, we review the approaches that have been proposed to quantify mechanosensation in living cells, with a specific focus on methodologies that enable higher experimental throughput. This aspect is crucial to fully understand the nuances of mechanosensation and how it impacts the physiology and pathology of living systems. We will discuss traditional methods for studying mechanosensing at the level of single cells, with particular attention to the activation of the mechanosensitive ion channel piezo1. Moreover, we will present recent attempts to push the analysis towards higher throughput.

Pancreatic adenocarcinoma (PDAC) is the predominant form of pancreatic cancer and one of the leading causes of cancer-related death worldwide, with an extremely poor prognosis after diagnosis. High mortality from PDAC arises partly due to late diagnosis resulting from a lack of early-stage biomarkers and due to chemotherapeutic drug resistance, which arises from a highly fibrotic stromal response known as desmoplasia. Desmoplasia alters tissue mechanics, which triggers changes in cell mechanosensing and leads to dysregulated transcriptional activity and disease phenotypes. Hydrogels are effective in vitro models to mimic mechanical changes in tissue mechanics during PDAC progression and to study the influence of these changes on mechanosensitive cell responses. Despite the complex biophysical changes that occur within the PDAC microenvironment, carefully designed hydrogels can very closely recapitulate these properties during PDAC progression. Hydrogels are relatively inexpensive, highly reproducible and can be designed in a humanised manner to increase their relevance for human PDAC studies. In vivo models have some limitations, including species-species differences, high variability, expense and legal/ethical considerations, which make hydrogel models a promising alternative. Here, we comprehensively review recent advancements in hydrogel bioengineering for developing our fundamental understanding of mechanobiology in PDAC, which is critical for informing advanced therapeutics.

[This corrects the article DOI: 10.1007/s12551-024-01233-2.].

Protein loops and structural domains are building blocks of molecular structure. They hold evolutionary memory and are largely responsible for the many functions and processes that drive the living world. Here, we briefly review two decades of phylogenomic data-driven research focusing on the emergence and evolution of these elemental architects of protein structure. Phylogenetic trees of domains reconstructed from the proteomes of organisms belonging to all three superkingdoms and viruses were used to build chronological timelines describing the origin of each domain and its embedded loops at different levels of structural abstraction. These timelines consistently recovered six distinct evolutionary phases and a most parsimonious evolutionary progression of cellular life. The timelines also traced the birth of domain structures from loops, which allowed to model their growth ab initio with AlphaFold2. Accretion decreased the disorder of the growing molecules, suggesting disorder is molecular size-dependent. A phylogenomic survey of disorder revealed that loops and domains evolved differently. Loops were highly disordered, disorder increased early in evolution, and ordered and moderate disordered structures were derived. Gradual replacement of loops with α-helix and β-strand bracing structures over time paved the way for the dominance of more disordered loop types. In contrast, ancient domains were ordered, with disorder evolving as a benefit acquired later in evolution. These evolutionary patterns explain inverse correlations between disorder and sequence length of loops and domains. Our findings provide a deep evolutionary view of the link between structure, disorder, flexibility, and function.

Aptamers are short oligonucleotides that bind specifically to various ligands and are characterized by their low immunogenicity, thermostability, and ease of labeling. Many biomedical applications of aptamers as biosensors and drug delivery agents are currently being actively researched. Selective affinity selection with exponential ligand enrichment (SELEX) allows to discover aptamers for a specific target, but it only provides information about the sequence of aptamers; hence other approaches are used for determining aptamer structure, aptamer-ligand interactions and the mechanism of action. The first one is in silico modelling that allows to infer likely secondary and tertiary structures and model their interactions with a ligand. The second approach is to use instrumental methods to study structure and aptamer-ligand interaction. In silico modelling and instrumental methods are complimentary and their combined use allows to eliminate some ambiguity in their respective results. This review examines both the advantages and limitations of in silico modelling and instrumental approaches currently used to study aptamers, which will allow researchers to develop optimal study designs for analyzing aptamer structure and ligand interactions.

The review deals with the application of Molecular Dynamics (MD) to the structure modeling of beta-amyloids (Aβ), currently classified as intrinsically disordered proteins (IDPs). In this review, we strive to relate the main advances in this area but specifically focus on the approaches and methodology. All relevant papers on the Aβ modeling are cited in the Tables in Supplementary Data, including a concise description of the applied approaches, sorted according to the types of the studied systems: modeling of the monomeric Aβ and Aβ aggregates. Similar sections focused according to the type of modeled object are present in the review. In the final part of the review, novel methods of general IDP modeling not confined to Aβ are described.

Supplementary information: The online version contains supplementary material available at 10.1007/s12551-024-01253-y.

In modern biological microscopy, the explosion of data volume and complexity highlights the urgent need for specialised data management support roles. While traditional microscopy focuses on visual data presentation, the rapid increase in big data acquisition and data mining demands advanced handling and analysis. This gap underscores the need for "dry lab microscopists" or data experts skilled in microscopy data management, software interoperability, and AI-driven solutions. Job markets reflect this demand, pointing to the necessity for dedicated training programs. Integrating these specialists into research institutions is crucial for addressing digital data challenges and maintaining high standards in data integrity and analysis. Their role is essential for advancing research in the data-driven era.