Biophysics and Physicobiology最新文献

Organoid, an organ-like tissue reproduced in a dish, has specialized, functional structures in three-dimensional (3D) space. Organoid development replicates the self-organizing process of each tissue development during embryogenesis but does not necessarily require external tissues, illustrating the autonomy of multicellular systems. Herein, we review the developmental processes of epithelial organoids, namely, the intestine, and optic-cup, with a focus on their mechanical aspects. Recent organoid studies have advanced our understanding of the mechanisms of 3D tissue deformation, including appropriate modes of deformation and factors controlling them. In addition, the autonomous nature of organoid development has also allowed us to access the stepwise mechanisms of deformation as organoids proceed through distinct stages of development. Altogether, we discuss the potential of organoids in unveiling the autonomy of multicellular self-organization from a mechanical point of view. This review article is an extended version of the Japanese article, Mechanics in Self-organizing Organoid Morphogenesis, published in SEIBUTSU BUTSURI Vol. 60, p.31-36 (2020).

During the repair of double-strand breaks (DSBs) in DNA, active mobilizations for conformational changes in chromosomes have been widely observed in eukaryotes, from yeast to animal and plant cells. DSB-damaged loci in the yeast genome showed increased mobility and relocation to the nuclear periphery. However, the driving forces behind DSB-induced chromatin dynamics remain unclear. In this study, mathematical models of normal and DSB-damaged yeast chromosomes were developed to simulate their structural dynamics. The effects of histone degradation in the whole nucleus and the change in the physical properties of damaged loci due to the binding of SUMOylated repair proteins were considered in the model of DSB-induced chromosomes based on recent experimental results. The simulation results reproduced DSB-induced changes to structural and dynamical features by which the combination of whole nuclear histone degradation and the rigid structure formation of repair protein accumulations on damaged loci were suggested to be primary contributors to the process by which damaged loci are relocated to the nuclear periphery.

Microbial rhodopsin is a ubiquitous membrane protein in unicellular microorganisms. Similar to animal rhodopsin, this protein consists of seven transmembrane helices and the chromophore retinal. However, unlike animal rhodopsin, microbial rhodopsin acts as not only a photosignal receptor but also a light-activated ion transporter and light-switchable enzyme. In this article, the third Cl^- pump microbial rhodopsin will be introduced. The physiological importance of Cl^- pumps has not been clarified. Despite this, their mechanisms, especially that of the first Cl^- pump halorhodopsin (HR), have been studied to characterize them as model proteins for membrane anion transporters. The third Cl^- pump defines a phylogenetic cluster distinct from other microbial rhodopsins. However, this Cl^- pump conserves characteristic residues for not only the Cl^- pump HR but also the H⁺ pump bacteriorhodopsin (BR). Reflecting close similarity to BR, the third Cl^- pump begins to pump H⁺ outwardly after single amino acid replacement. This mutation activates several residues that have no roles in the original Cl^- pump function but act as important H⁺ relay residues in the H⁺ pump mutant. Thus, the third Cl^- pump might be the model protein for functional differentiation because this rhodopsin seems to be the Cl^- pump occurring immediately after functional differentiation from the BR-type H⁺ pump.

We recently proposed a computational procedure to simulate the dissociation of protein/ligand complexes using the dissociation Parallel Cascade Selection Molecular Dynamics simulation (dPaCS-MD) method and to analyze the generated trajectories using the Markov state model (MSM). This procedure, called dPaCS-MD/MSM, enables calculation of the dissociation free energy profile and the standard binding free energy. To examine whether this method can reproduce experimentally determined binding free energies for a variety of systems, we used it to investigate the dissociation of three protein/ligand complexes: trypsin/benzamine, FKBP/FK506, and adenosine A_{2 A} receptor/T4E. First, dPaCS-MD generated multiple dissociation pathways within a reasonable computational time for all the complexes, although the complexes differed significantly in the size of the molecules and in intermolecular interactions. Subsequent MSM analyses produced free energy profiles for the dissociations, which provided insights into how each ligand dissociates from the protein. The standard binding free energies obtained by dPaCS-MD/MSM are in good agreement with experimental values for all the complexes. We conclude that dPaCS-MD/MSM can accurately calculate the binding free energies of these complexes.

Successful synaptic integration is said to require that multiple excitatory postsynaptic potentials (EPSPs) occur almost simultaneously over a short period of time, so that they overlap and increase. However, if brain function is based on a chain of successful synaptic integrations, then constraints on the spacing of multiple EPSP generation must be released to allow for a higher probability of successful synaptic integration. This paper demonstrates that Ca²⁺ ions retained in spines after EPSP generation polarize spine neck fluid and dendritic fluid as a dielectric medium, that polarization is transmitted through dendrites to the cell body (soma), that polarization is enhanced by the addition of polarization from each spine, and that I propose that synaptic integration is successful when the membrane potential, as determined by the enhanced polarization and membrane capacitance, reaches the threshold of voltage-gated Na⁺ channels. Furthermore, the approach taken in this study suggests that a single neuron can integrate synapses for many combinations of synaptic inputs, that successful synaptic integration depends on spine neck capacitance and spine head size, and that spines farther from the soma are able to contribute to successful synaptic integration, and led to the elucidation of a number of important issues, including the fact that inhibitory post-synapses on dendrites suppress s effectively synaptic integration.