Biophysical reviews最新文献

The flow sensing endothelial cell lining of blood and lymphatic vessels is essential in vertebrates. While the mechanisms are still mysterious in many regards, several critical components became apparent through molecular biology studies. In this article, we focus on PIEZO1, which forms unusual force-sensing ion channels capable of rapid transduction of force into biological effect. We describe current knowledge and emerging challenges. We suggest the idea of using computation to construct the flow sensing mechanism of endothelium to advance understanding, develop testable hypotheses and potentially design novel therapeutic strategies and synthetic flow sensing devices.

Intracellular transport is essential for maintaining cellular function. This process is driven by different mechanisms in prokaryotic and eukaryotic cells. In small prokaryotic cells, diffusion is the primary means of transport, while larger eukaryotic cells also rely on active transport by molecular motors such as kinesin and dynein. Recently, it has become evident that, in addition to diffusion based on thermal fluctuations (Brownian motion), which was conventionally considered a diffusion mechanism within living cells, nonthermal fluctuations generated by metabolic activities play a crucial role in intracellular diffusion. Similarly, while molecular motors have been proposed to exploit thermal fluctuations in the environment following the direct observation and manipulation of single molecules, they have also been reported to utilize nonthermal fluctuations in recent years. This review begins with a brief overview of the historical knowledge of diffusive intracellular transport, which has been extended from the thermal fluctuations to the nonthermal fluctuations generated by metabolic activity. It then introduces recent findings on how nonthermal fluctuations accelerate the motion of molecular motors and discusses future perspectives on the general effects of these fluctuations on molecules in living cells.

Extreme value analysis (EVA) is a statistical method that studies the properties of extreme values of datasets, crucial for fields like engineering, meteorology, finance, insurance, and environmental science. EVA models extreme events using distributions such as Fréchet, Weibull, or Gumbel, aiding in risk prediction and management. This review explores EVA's application to nanoscale biological systems. Traditionally, biological research focuses on average values from repeated experiments. However, EVA offers insights into molecular mechanisms by examining extreme data points. We introduce EVA's concepts with simulations and review its use in studying motor protein movements within cells, highlighting the importance of in vivo analysis due to the complex intracellular environment. We suggest EVA as a tool for extracting motor proteins' physical properties in vivo and discuss its potential in other biological systems. While there have been only a few applications of EVA to biological systems, it holds promise for uncovering hidden properties in extreme data, promoting its broader application in life sciences.

Living systems are complex and hierarchical, with diverse components at different scales, yet they sustain themselves, grow, and evolve over time. How can a theory of such complex biological states be developed? Here we note that for a hierarchical biological system to be robust, it must achieve consistency between micro-scale (e.g., molecular) and macro-scale (e.g., cellular) phenomena. This allows for a universal theory of adaptive change in cells based on biological robustness and consistency between cellular growth and molecular replication. Here, we show how adaptive changes in high-dimensional phenotypes (biological states) are constrained to low-dimensional space, leading to the derivation of a macroscopic law for cellular states. The theory is then extended to evolution, leading to proportionality between evolutionary and environmental responses, as well as proportionality between phenotypic variances due to noise and due to genetic changes. The universality of the results across several models and experiments is demonstrated. Then, by further extending the theory of evolutionary dimensional reduction to multicellular systems, the relationship between multicellular development and evolution, in particular, the developmental hourglass, is demonstrated. Finally, the possibility of collapse of dimensional reduction under nutrient limitation is discussed.

During cell division, the network of microtubules undergoes massive rearrangement to self-organize into the spindle, a bipolar structure essential for accurate chromosome segregation. This structure ensures the stable transmission of the genome from the mother cell to two daughter cells, yet the process by which the ordered architecture emerges from a collection of protein "parts" remains a mystery. In this review, we focus on several key spindle proteins, describing how they move, crosslink, and grow microtubules in vitro and contribute to the spindle's structural organization. We categorize these proteins into groups, such as transporters, bundlers, and nucleators, to highlight their functional roles. We also present an advanced perspective on the spindle's complex polymer architecture and its temporal assembly order in cellular contexts. This in situ level information should guide the minimal reconstitution of the spindle, helping to elucidate the biophysical principles underlying essential cytoskeletal self-organization.

Amyloid fibrils, historically stigmatized due to their association with diseases like Alzheimer's and Parkinson's, are now recognized as a distinct class of functional proteins with extraordinary potential. These highly ordered, cross-β-sheet protein aggregates are found across all domains of life, playing crucial physiological roles. In bacteria, functional amyloids like curli fibers are essential for surface adhesion, biofilm formation, and viral DNA packaging. Fungal prions exploit amyloid conformations to regulate translation, metabolism, and virulence, while mammalian amyloids are integral to melanin synthesis, hormone storage, and antimicrobial defense. The stability and hydrophobic nature of amyloid scaffolds underpin these diverse biological functions. Beyond their natural roles, amyloid fibrils offer unique capabilities in biomedicine, nanotechnology, and materials science. Their exceptional mechanical strength and biocompatibility make them ideal for controlled drug delivery, tissue engineering scaffolds, and enzyme immobilization. The intrinsic fluorescence and optical properties of certain amyloids open up innovative applications in biosensors, molecular probes, and optoelectronic devices. Furthermore, amyloid fibrils can template metal nanowires, enhance conducting materials, and form nanocomposites by integrating with polymers. This newfound appreciation for the functional diversity of amyloids has ignited intense research efforts to elucidate their molecular mechanisms, stability, and tunable properties. By unraveling the structural intricacies of functional amyloids, researchers aim to harness their remarkable attributes for groundbreaking biomedical therapies, advanced nanomaterials, and sustainable biotechnological innovations. This review explores the transformative journey of amyloids from pathological entities to biotechnological marvels, highlighting their vast potential across agriculture, environmental remediation, and industrial processes.

Since the first observations of chromosome segregation over 150 years ago, efforts to observe the forces that drive mitosis have evolved alongside advances in microscopy. The mitotic spindle acts as the major generator of force through the highly regulated polymerization and depolymerization of microtubules as well as associated motor proteins. Centromeric chromatin, along with associated proteins including cohesin and condensin, is organized to resist these forces and ensure accurate chromosome segregation. Microtubules and centromeric chromatin join at the kinetochore, a complex protein superstructure. Ongoing research into the forces generated at the kinetochore-microtubule interface has resulted in a range of estimates for forces necessary to separate chromosomes, from tens to hundreds of piconewtons. Still, the exact magnitude and regulation of these forces remain areas of continuing investigation. Determining the precise forces involved in chromosome segregation is hindered by limitations of current measurement techniques, but advances such as optical tweezers combined with fluorescence microscopy are promising for future research.

The tumor microenvironment (TME) is a complex and dynamic network that significantly influences cancer progression. Understanding its intricate components, including the extracellular matrix (ECM), stromal cells, immune cells, and vascular endothelial cells, is crucial for developing effective cancer therapies. Conventional diagnostic methods, while essential, have limitations in sensitivity, specificity, and invasiveness. Label-free multimodal nonlinear optical (MNLO) microscopy offers a promising alternative, enabling detailed imaging without external labels. Techniques such as second harmonic generation (SHG), third harmonic generation (THG), coherent anti-Stokes Raman scattering (CARS), and two-photon fluorescence (TPF) provide complementary insights into the TME. SHG is particularly effective for imaging collagen fibers, while CARS highlights lipid-rich structures, and THG and TPF offer high-resolution imaging of cellular and subcellular structures. These modalities reveal crucial information about tumor progression, including changes in collagen organization and lipid metabolism, and allow for the study of cellular interactions and ECM remodeling. Multimodal setups, combining SHG, CARS, THG, and TPF, enable comprehensive analysis of the TME, facilitating the identification of early-stage cancerous changes and tracking of tumor progression. Despite the advantages of MNLO microscopy, such as reduced photodamage and the ability to image live tissues, challenges remain, including the complexity and cost of the setups. Addressing these challenges through technological advancements and optimization can enhance the applicability of MNLO microscopy in clinical diagnostics and cancer research, ultimately contributing to improved cancer diagnosis, prognosis, and treatment strategies.

A personal note from the 2023-2024 President of the Biophysical Society of Japan (BSJ) on the role and activities of the BSJ in preparation for the 2024 IUPAB Congress in Kyoto.