Biology subjects

Iwaki, M.

Publications and source records attributed to Iwaki, M..

7 recordsLinked to original sources

bioRxiv2026

Comparative genome analysis of Corynebacterium ulcerans Japanese isolates revealed domestically and globally diverse geographical distribution of the organism of different types.

Corynebacterium ulcerans is a zoonotic pathogen causing infections in humans that are clinically indistinguishable from those of Corynebacterium diphtheriae. In many developed countries, companion animals such as dogs and cats, are the predominant sources of infection by C. ulcerans, as is the case in Japan. To date, we have collected 106 Japanese clinical and domestic animal isolates of C. ulcerans and a recently branched species, C. ramonii, most of which were isolated from humans and cats. In the present study, we performed a comparative analysis of whole-genome sequences from Japanese isolates and 597 published isolates from Japan and outside Japan. The Japanese isolates were divided into two distinct lineages: C. ulcerans and C. ramonii. The MLST types of C. ulcerans Japanese isolates exhibited a unique distribution pattern, with one major type (ST337) accounting for 69.0%, which is very rare in Europe. In addition to Japan, distinct MLST pattern compositions were observed across geographically distinct regions. The sequence types were associated with lysogenized prophage types that encode the diphtheria toxin (tox) gene and were partially associated with toxin production under certain conditions. Through SNV analysis, transmission from animals to humans has been suggested in some clinical cases. Significance StatementBy analyzing more than 700 genomes, we demonstrate striking geographic differences in multilocus sequence types and toxigenic prophage compositions between Japanese and European isolates. Notably, we identify the predominance of sequence type ST337 in Japan, a lineage that is rare in Europe, and show that prophage types encoding the diphtheria toxin are closely associated with specific sequence types and toxin production phenotypes. Our single-nucleotide variant analyses further provide genomic evidence supporting zoonotic transmission between companion animals and humans in several clinical cases.

microbiology↗

bioRxiv2025

Distinct dermal fibroblasts direct mechano-chemical signaling to the epidermis during pregnancy

Dermal fibroblasts alter extracellular matrix (ECM) and tissue mechanics dynamically in wound healing and fibrosis, however, are understudied in healthy skin remodeling across life stages. Here, by conducting spatio-temporal transcriptomics, we identified Cdh4+ dermal fibroblast subpopulation that remodels ECM and converts mechano-to-chemical signals to promote epidermal stem cell proliferation in expanding abdominal skin of pregnant mice. Mechanistically, Cdh4+ fibroblasts produce a pregnancy-responsive matrisome, resulting in denser and stiffer dermal fibrils. These fibroblasts then sense the stiffened substrate and convert the mechanical input into a chemical output via the YAP1-TGF{beta}2 axis, leading to the proliferation of epidermal stem cells via TGF{beta} receptor in the expanding skin. Thus, Cdh4+ fibroblasts fine-tune the dermal mechanofield and act as a mechanical-to-chemical signal conversion hub in healthy skin expansion.

developmental biology↗

bioRxiv2025

Stall force measurement of the kinesin-3 motor KIF1A using a programmable DNA origami nanospring

DNA origami technology is a method for designing and constructing nanoscale structures using DNA, and it is being applied across various fields. This technology was advanced by developing the nanospring (NS), a fluorescently visible molecular spring that quantifies forces through its extension and has been used to measure myosin-generated forces. This study aims to measure the force exerted by the kinesin-3 motor protein KIF1A, mutations of which cause KIF1A-associated neurological disorder (KAND) and are associated with reduced force and motility. Unlike kinesin-1, KIF1A detaches easily under perpendicular loads, which can occur in optical tweezers experiments. By applying force parallel to the microtubule using the NS, we were able to precisely measure the stall force even for KAND mutants, for which such measurements are typically challenging. This result highlights the potential of the NS as a new tool for force spectroscopy in biophysics.

biophysics↗

bioRxiv2023

Dynamic coordination of the lever-arm swing of human myosin II in thick filaments on actin

Muscle myosins work in motor ensembles and must adapt their power stroke in response to mechanical actions by surrounding motors. Understanding the coordination of power strokes is essential for bridging microscopic molecular functions and macroscopic muscle contractions, but the details of this phenomenon remain elusive. Here we used high-speed atomic force microscopy to visualize the individual dynamics (lever-arm swing) of the myosin head bound to actin in DNA origami-based synthetic thick filaments. We observed spatially local lever-arm coordination, and our three-dimensional numerical model explained how mechanical communication between myosins achieved coordination. In a sarcomere model, the local coordination was spatially periodic and propagated toward the contraction direction. We confirmed that a structural mismatch between myosin head spacing (42.8 nm) and the actin helical pitch (37 nm) caused the coordination while improving contraction speed and energy efficiency. Our findings reveal a key physical basis of efficient muscle contraction.

biophysics↗

bioRxiv2021

The synergic role of actomyosin architecture and biased detachment in muscle energetics: insights in cross bridge mechanism beyond the lever-arm swing

Muscle energetics reflects the ability of myosin motors to convert chemical energy into mechanical energy. How this process takes place remains one of the most elusive questions in the field. Here we combined experimental measurements of in vitro sliding velocity based on DNA-origami built filaments carrying myosins with different lever arm length and simulations based on a Monte-Carlo model which accounts for three basic components: (i) the geometrical hindrance, (ii) the mechano-sensing mechanism, and (iii) the biased kinetics for stretched or compressed motors. The model simulations showed that the geometrical hindrance due to acto-myosin spatial mismatching and the preferential detachment of compressed motors are synergic in generating the rapid increase in the ATP-ase rate from isometric to moderate velocities of contraction, thus acting as an energy-conservation strategy in muscle contraction. The velocity measurements on a DNA-origami filament that preserves the motors distribution showed that geometrical hindrance and biased detachment generate a non-zero sliding velocity even without rotation of the myosin lever-arm, which is widely recognized as the basic event in muscle contraction. Because biased detachment is a mechanism for the rectification of thermal fluctuations, in the Brownian-ratchet framework, we predict that it requires a non-negligible amount of energy to preserve the second law of thermodynamics. Taken together, our theoretical and experimental results elucidate non-conventional components in the chemo-mechanical energy transduction in muscle.

biophysics↗

bioRxiv2019

Direct visualization of human myosin II force generation using DNA origami-based thick filaments

Muscle contraction can be explained by the swinging lever-arm model. However, the dynamic features of how the myosin head swings the lever-arm and its initial interactions with actin are not well understood even though they are essential for the muscle force generation, contraction speed, heat production, and response to mechanical perturbations. This is because myosin heads during force generation have not been directly visualized. Here, we engineered thick filaments composed of DNA origami and recombinant human muscle myosin, and directly visualized the heads during force generation using nanometer-precision single-molecule imaging. We found that when the head diffuses, it weakly interacts with actin filaments and then strongly binds preferentially to the forward region as a Brownian ratchet. Upon strong binding, the head two-step lever-arm swing dominantly halts at the first step and occasionally reverses direction. These results can explain all mechanical characteristics of muscle contraction and suggest that our DNA origami-based assay system can be used to dissect the mechanistic details of motor proteins.

biophysics↗

bioRxiv2017

Application of the fluctuation theorem for non-invasive force measurement in living neuronal axons

Although its importance is recently widely accepted, force measurement has been difficult in living biological systems, mainly due to the lack of the versatile non-invasive force measurement methods. The fluctuation theorem, which represents the thermodynamic properties of small fluctuating non-equilibrium systems, has been applied to the analysis of the thermodynamic properties of motor proteins in vitro. Here, we extend it to the axonal transport (displacement) of endosomes. The distribution of the displacement fluctuation had three or four distinct peaks around multiples of a unit value, which the fluctuation theorem can convert into the drag force exerted on the endosomes. The results demonstrated that a single cargo vesicle is conveyed by one to three or four units of force production.

biophysics↗