Biophysics and Physicobiology最新文献

While it is often believed that the origins of life required participation of early biomolecules, it has been recently proposed that "non-biomolecules", which would have been just as, if not more, abundant on early Earth, could have played a part. In particular, recent research has highlighted the various ways by which polyesters, which do not participate in modern biology, could have played a major role during the origins of life. Polyesters could have been synthesized readily on early Earth through simple dehydration reactions at mild temperatures involving abundant "non-biological" alpha hydroxy acid (AHA) monomers. This dehydration synthesis process results in a polyester gel, which upon further rehydration, can assemble into membraneless droplets proposed to be protocell models. These proposed protocells can provide functions to a primitive chemical system, such as analyte segregation or protection, which could have further led to chemical evolution from prebiotic chemistry to nascent biochemistry. Here, to further shed light into the importance of "non-biomolecular" polyesters at the origins of life and to highlight future directions of study, we review recent studies which focus on primitive synthesis of polyesters from AHAs and assembly of these polyesters into membraneless droplets. Specifically, most of the recent progress in this field in the last five years has been led by laboratories in Japan, and these will be especially highlighted. This article is based on an invited presentation at the 60th Annual Meeting of the Biophysical Society of Japan held in September, 2022 as an 18th Early Career Awardee.

Near-field scanning optical microscopy (NSOM) is a super-resolution optical microscopy based on nanometrically small near-field light at a metallic tip. It can be combined with various types of optical measurement techniques, including Raman spectroscopy, infrared absorption spectroscopy, and photoluminescence measurements, which provides unique analytical capabilities to a variety of scientific fields. In particular, to understand nanoscale details of advance materials and physical phenomena, NSOM has been often adopted in the fields of material science and physical chemistry. However, owing to the recent critical developments showing the great potential for biological studies, NSOM has also recently gained much attention in the biological field. In this article, we introduce recent developments made in NSOM, aiming at biological applications. The drastic improvement in the imaging speed has shown a promising application of NSOM for super-resolution optical observation of biological dynamics. Furthermore, stable imaging and broadband imaging were made possible owing to the advanced technologies, which provide a unique imaging method to the biological field. As NSOM has not been well exploited in biological studies to date, several rooms need to be explored to determine its distinct advantages. We discuss the possibility and perspective of NSOM for biological applications. This review article is an extended version of the Japanese article, Development of Near-field Scanning Optical Microscopy toward Its Application for Biological Studies, published in SEIBUTSU BUTSURI Vol. 62, p. 128-130 (2022).

Mitochondria play an important role in energy conversion as well as in intracellular calcium (Ca²⁺) storage. Ca²⁺ uptake from the cytosol to the mitochondria is mediated by the calcium uniporter, which functions as a Ca²⁺ ion channel. However, the molecular composition of this uniporter has remained unclear until recently. The Ca²⁺ ion channel consists of seven subunits. The yeast reconstitution technique revealed that the mitochondrial calcium uniporter (MCU) and essential MCU regulatory element (EMRE) are the core subunits of the complex. Furthermore, detailed structure-function analyses of the core subunits (MCU and EMRE) were performed. In this review, the regulatory mechanism of mitochondrial Ca²⁺ uptake is discussed.

The high-speed atomic force microscopy (HS-AFM) is a unique and prominent method to observe structural dynamics of biomolecules at single molecule level at near-physiological condition. To achieve high temporal resolution, the probe tip scans the stage at high speed which can cause the so-called parachuting artifact in the HS-AFM images. Here, we develop a computational method to detect and remove the parachuting artifact in HS-AFM images using the two-way scanning data. To merge the two-way scanning images, we employed a method to infer the piezo hysteresis effect and to align the forward- and backward-scanning images. We then tested our method for HS-AFM videos of actin filaments, molecular chaperone, and duplex DNA. Together, our method can remove the parachuting artifact from the raw HS-AFM video containing two-way scanning data and make the processed video free from the parachuting artifact. The method is general and fast so that it can easily be applied to any HS-AFM videos with two-way scanning data.

To completely treat and ultimately prevent dementia, it is essential to elucidate its pathogenic mechanisms in detail. There are two major hypotheses for the pathogenesis of Alzheimer's dementia: the β-amyloid (Aβ) hypothesis and the tau hypothesis. The modified amyloid hypothesis, which proposes that toxic oligomers rather than amyloid fibrils are the essential cause, has recently emerged. Aβ peptides [Aβ(1-40) and Aβ(1-42)] form highly insoluble aggregates in vivo and in vitro. These Aβ aggregates contain many polymorphisms, whereas Aβ peptides are intrinsically disordered in physiological aqueous solutions without any compact conformers. Over the last three decades, solid-state nuclear magnetic resonance (NMR) has greatly contributed to elucidating the structure of each polymorph, while solution NMR has revealed the dynamic nature of the transient conformations of the monomer. Moreover, several methods to investigate the aggregation process based on the observation of magnetization saturation transfer have also been developed. The complementary use of NMR methods with cryo-electron microscopy, which has rapidly matured, is expected to clarify the relationship between the amyloid and molecular pathology of Alzheimer's dementia in the near future. This review article is an extended version of the Japanese article, Insights into the Mechanisms of Oligomerization/Fibrilization of Amyloid β Peptide from Nuclear Magnetic Resonance, published in SEIBUTSU BUTSURI Vol. 62, p. 39-42 (2022).