Environment-Sensitive Intelligent Self-Reproducing Artificial Cell with a Modification-Active Lipo-Deoxyribozyme

As a supramolecular micromachine with information flow, a giant vesicle (GV)-based artificial cell that exhibits a linked proliferation between GV reproduction and internal DNA amplification has been explored in this study. The linked proliferation is controlled by a complex consisting of GV membrane-intruded DNA with acidic amphiphilic catalysts, working overall as a lipo-deoxyribozyme. Here, we investigated how a GV-based artificial cell containing this lipo-deoxyribozyme responds to diverse external and internal environments, changing its proliferative dynamics. We observed morphological changes (phenotypic expression) in GVs induced by the addition of membrane precursors with different intervals of addition (starvation periods). First, we focused on a new phenotype, the “multiple tubulated” form, which emerged after a long starvation period. Compared to other forms, the multiple tubulated form is characterized by a larger membrane surface with a heavily cationic charge. A second consideration is the effect of the chain length of encapsulated DNA on competitive proliferation. The competitive proliferation among three different species of artificial cells containing different lengths of DNA was investigated. The results clearly showed a distinct intervention in the proliferation dynamics of the artificial cells with each other. In this sense, our GV-based artificial cell can be regarded as an intelligent supramolecular machine responding to external and internal environments, providing a new concept for developing molecular machines and robotics

A case of hypopharyngeal cancer with stenosis, perforation, and pyogenic spondylitis development after chemoradiotherapy

Introduction: Chemoradiotherapy plays an important role in preserving function and morphology in head and neck cancer. However, in a few cases, chemoradiotherapy has been shown to result in late complications, such as hypopharyngeal perforation, which is very rare. Presentation of case: A 65-year-old man, who had undergone chemoradiotherapy for hypopharyngeal cancer 30 months previously, presented with high fever and neck pain. He subsequently developed hypopharyngeal stenosis, hypopharyngeal perforation, and a retropharyngeal abscess followed by pyogenic spondylitis. He underwent surgical treatment (resection with reconstruction) and was administered an antibacterial agent and steroids for an extended period. This treatment regimen was successful, and the patient has survived disease-free without symptoms. Discussion: Chemoradiotherapy-induced hypopharyngeal perforation is an extremely rare condition. In the present case, the perforation was large (2 cm), and the hypopharyngeal cavity was originally constricted. Pharyngeal reconstruction with a jejunal autograft was therefore necessary. Through the present case, we reconfirmed that although the primary purpose of chemoradiotherapy is organ preservation, it can also lead to organ destruction and fatal complications. It is important that physicians be aware of the possibility of hypopharyngeal perforation so as to avoid delayed diagnosis and treatment of similar rare cases. Conclusion: Hypopharyngeal perforation can sometimes be fatal because it can lead to pyogenic spondylitis. Suitable surgical techniques and appropriate doses of antibacterial agents for long-term use were appropriate treatments for the patient in this case

Evolution of Proliferative Model Protocells Highly Responsive to the Environment

In this review, we discuss various methods of reproducing life dynamics using a constructive approach. An increase in the structural complexity of a model protocell is accompanied by an increase in the stage of reproduction of a compartment (giant vesicle; GV) from simple reproduction to linked reproduction with the replication of information molecules (DNA), and eventually to recursive proliferation of a model protocell. An encounter between a plural protic catalyst (C) and DNA within a GV membrane containing a plural cationic lipid (V) spontaneously forms a supramolecular catalyst (C@DNA) that catalyzes the production of cationic membrane lipid V. The local formation of V causes budding deformation of the GV and equivolume divisions. The length of the DNA strand influences the frequency of proliferation, associated with the emergence of a primitive information flow that induces phenotypic plasticity in response to environmental conditions. A predominant protocell appears from the competitive proliferation of protocells containing DNA with different strand lengths, leading to an evolvable model protocell. Recently, peptides of amino acid thioesters have been used to construct peptide droplets through liquid–liquid phase separation. These droplets grew, owing to the supply of nutrients, and were divided repeatedly under a physical stimulus. This proposed chemical system demonstrates a new perspective of the origins of membraneless protocells, i.e., the “droplet world” hypothesis. Proliferative model protocells can be regarded as autonomous supramolecular machines. This concept of this review may open new horizons of “evolution” for intelligent supramolecular machines and robotics

Physicochemical Cause and Effect Observed in DNA Length-Dependent Division of Protocell as the Primitive Flow of Information

In the prebiotic era, physicochemical cause and effect served as the primitive flow of information for protocells. Our recent study claimed that the manners and frequencies of self-reproduction of giant vesicle (GV) -based model protocells were regulated by the incorporated DNA-length, and not the base-pair sequence due to the presence of a supramolecular catalyst (lipo-deoxyribozyme) composed of DNA and lipophilic catalysts. The DNA-length dependent dynamics of the self-reproducing GVs containing different length of DNA were examined by three independent experiments; Population analysis by flow cytometric measurements, counting of　increased numbers of protocells and direct morphological observation of a single GV by confocal microscopy. These results may shed light on the information system in the prebiotic stage, when the central dogma was not established. Notably, recent reports have revealed the possible influence of DNA length on the activation of living cells through the complexation of DNA to an enzyme in non-sequential aggregation manner.This work was supported by JSPS KAKENHI (Grant Numbers JP25103009, JP16K05759 and JP17H04876), ‘Platform for Dynamic Approaches to Living System’ at the University of Tokyo, Kanagawa University Grant for Joint Research, and the Yoshida Scholarship Foundation

Oscillatory Motion of an Organic Droplet Reflecting a Reaction Scheme

An organic droplet containing thymol acetate (TA) floating on a sodium dodecyl sulfate aqueous phase was examined to develop a novel self-propelled object based on reaction kinetics. Two types of oscillatory motion, without back-and-forth motion (Osc I) and with back-and-forth motion (Osc II), were observed by varying the pH of the aqueous phase. The oscillation frequency reached its maximum at pH 9.6, coinciding with the occurrence of Osc II. The kinetics of the hydrolysis of TA as a reactant and the acid–base equilibrium between thymol (TOH) and the thymolate ion (TO–) as products were evaluated experimentally. The driving force of motion was discussed on the basis of the interfacial tension. The pH dependence of the oscillation frequency and the selection of Osc I or II were attributed to the equilibrium between the TOH and TO–. These results highlight the possibility of designing self-propulsion systems by considering reaction kinetics and chemical properties