Triggerable Protocell Capture in Nanoparticle-Caged Coacervate Microdroplets

[Image: see text] Controlling the dynamics of mixed communities of cell-like entities (protocells) provides a step toward the development of higher-order cytomimetic behaviors in artificial cell consortia. In this paper, we develop a caged protocell model with a molecularly crowded coacervate interior surrounded by a non-cross-linked gold (Au)/poly(ethylene glycol) (PEG) nanoparticle-jammed stimuli-responsive membrane. The jammed membrane is unlocked by either exogenous light-mediated Au/PEG dissociation at the Au surface or endogenous enzyme-mediated cleavage of a ketal linkage on the PEG backbone. The membrane assembly/disassembly process is used for the controlled and selective uptake of guest protocells into the caged coacervate microdroplets as a path toward an all-water model of triggerable transmembrane uptake in synthetic protocell communities. Active capture of the guest protocells stems from the high sequestration potential of the coacervate interior such that tailoring the surface properties of the guest protocells provides a rudimentary system of protocell sorting. Our results highlight the potential for programming surface-contact interactions between artificial membrane-bounded compartments and could have implications for the development of protocell networks, storage and delivery microsystems, and microreactor technologies

Orientational behaviors of silk fibroin hydrogels

In this study, a novel shear-induced silk fibroin hydrogel with three-dimensional (3D) anisotropic and oriented gel skeleton/network morphology is presented. Amphipathic anionic and nontoxic sodium surfactin is blended with the silk fibroin to decrease its gelation time during the mechanical shearing process. The fibroin/surfactin blended solutions undergo a facial shearing process to accomplish a solâ gel transition within one hour. The dynamic solâ gel transition kinetic analysis, gel skeleton/network morphology, and mechanical property measurements are determined in order to visualize the fibroin/surfactin solâ gel transition during the shearing process and its resulting hydrogel. The results demonstrate that there is significant b-sheet assembly from random coil conformations in the fibroin/surfactin blended system during the facile shearing process. The silk fibroin b-sheets further transform into a fibrous large-scale aggregation with orientational and parallel arrangements to the shearing direction. The shear-induced fibroin/ surfactin hydrogel exhibits notable anisotropic and oriented 3D skeleton/network morphology and a significant mechanical compressive strength in proportion to the shearing stress, compared with the control fibroin/surfactin hydrogel undergoing no shearing process. Due to its oriented gel skeleton/network structure and significantly enhanced mechanical properties, the shear-induced fibroin/ surfactin gel may be suitable as a biomaterial in 3D oriented tissue regeneration, including for nerves, the cultivation of bone cells, and the repair of defects in muscle and ligament tissues.The work is supported by National Natural Science Foundation of China (Grant No. 51373114), PAPD and College Nature Science Research Project of Jiangsu Province, China (Grant No. 15KJA540001). S. C. Kundu holds ERA Chair Full Professor of European Commission Programme (RoReCaST) at 3Bs Research Group, University of Minho, Portugal.info:eu-repo/semantics/publishedVersio

Silk Fibroin/Polyvinyl Pyrrolidone Interpenetrating Polymer Network Hydrogels

Silk fibroin hydrogel is an ideal model as biomaterial matrix due to its excellent biocompatibility and used in the field of medical polymer materials. Nevertheless, native fibroin hydrogels show poor transparency and resilience. To settle these drawbacks, an interpenetrating network (IPN) of hydrogels are synthesized with changing ratios of silk fibroin/N-Vinyl-2-pyrrolidonemixtures that crosslink by H2O2 and horseradish peroxidase. Interpenetrating polymer network structure can shorten the gel time and the pure fibroin solution gel time for more than a week. This is mainly due to conformation from the random coil to the β-sheet structure changes of fibroin. Moreover, the light transmittance of IPN hydrogel can be as high as more than 97% and maintain a level of 90% within a week. The hydrogel, which mainly consists of random coil, the apertures inside can be up to 200 μm. Elastic modulus increases during the process of gelation. The gel has nearly 95% resilience under the compression of 70% eventually, which is much higher than native fibroin gel. The results suggest that the present IPN hydrogels have excellent mechanical properties and excellent transparency.This work was supported by The National Key Research and Development Program of China (Grant No. 2017YFC1103602), National Natural Science Foundation of China (Grant No. 51373114, 51741301), PAPD and Nature Science Foundation of Jiangsu, China (Grant No. BK20171239, BK20151242).info:eu-repo/semantics/publishedVersio

Spontaneous Membranization in a Silk-Based Coacervate Protocell Model

Molecularly crowded coacervate micro‐droplets are useful protocell constructs but the absence of a physical membrane limits their application as cytomimetic models. Auxiliary surface‐active agents have been harnessed to stabilize the coacervate droplets by irreversible shell formation but endogenous processes of reversible membranization have received minimal attention. Herein, we describe a dynamic alginate/silk coacervate‐based protocell model in which membrane‐less droplets are reversibly reconfigured and inflated into semipermeable coacervate vesicles by spontaneous self‐organization of amphiphilic silk polymers at the droplet surface under non‐neutral charge conditions in the absence of auxiliary agents. We show that membranization can be reversibly controlled endogenously by programming the pH within the protocells using an antagonistic enzyme system such that structural reconfigurations in the protocell microstructure are coupled to the trafficking of water‐soluble solutes. Our results open new perspectives in the design of hybrid protocell models with dynamical structural properties

Natural Non-Mulberry Silk Nanoparticles for Potential-Controlled Drug Release

Natural silk protein nanoparticles are a promising biomaterial for drug delivery due to their pleiotropic properties, including biocompatibility, high bioavailability, and biodegradability. Chinese oak tasar Antheraea pernyi silk fibroin (ApF) nanoparticles are easily obtained using cations as reagents under mild conditions. The mild conditions are potentially advantageous for the encapsulation of sensitive drugs and therapeutic molecules. In the present study, silk fibroin protein nanoparticles are loaded with differently-charged small-molecule drugs, such as doxorubicin hydrochloride, ibuprofen, and ibuprofen-Na, by simple absorption based on electrostatic interactions. The structure, morphology and biocompatibility of the silk nanoparticles in vitro are investigated. In vitro release of the drugs from the nanoparticles depends on charge-charge interactions between the drugs and the nanoparticles. The release behavior of the compounds from the nanoparticles demonstrates that positively-charged molecules are released in a more prolonged or sustained manner. Cell viability studies with L929 demonstrated that the ApF nanoparticles significantly promoted cell growth. The results suggest that Chinese oak tasar Antheraea pernyi silk fibroin nanoparticles can be used as an alternative matrix for drug carrying and controlled release in diverse biomedical applications

The effect of Baduanjin Qigong combined with five-elements music on anxiety and quality of sleep in asymptomatic patients with COVID-19 infection: A randomised controlled trial

Background: Infections of Coronavirus Disease-2019 (COVID-19) and the subsequent quarantine can culminate in anxious mood and sleep disturbances. The objective of this clinical trial was to investigate the effect of traditional Qigong with music therapy on relieving anxiety and improving the quality of sleep in Chinese adults with COVID-19 infection. Methods: A total of 200 asymptomatic COVID-19 infected patients were randomly assigned into two groups during their quarantine period in Chongming Island, Shanghai. The patients in the treatment group daily received Baduanjin Qigong, five-elements music therapy and routine care, while the patients in the control group only took the routine care. The primary outcome was anxiety levels measured by the 7-item Generalized Anxiety Disorder scale (GAD-7). Secondary outcomes included the quality of sleep measured by the Jenkins Sleep Scale (JSS), the degree of depression measured by the Patient Health Questionnaire (PHQ-9), as well as the self-efficacy in the Perceived Health Competence Scale (PHCS). An online questionnaire was given to all participants on the day of arrival to determine the baseline for all outcomes and then given again on the day of discharge. A one-way analysis of covariance was used to analyze the differences between the two groups after intervention. Results: At the end of the intervention, 177 (88.5%) patients finished the questionnaire. Patients in the treatment group had clearly decreased GAD-7 scores (MD = 2.7, 95% CI = 2.3, 3.2) after the daily exercise and music. Patients in the control group had little changes in the GAD-7 (MD = −0.2, 95%CI = −0.7, 0.3, P = 0.07), as well as the PHQ-9 (MD = 0.1, 95%CI = −0.5, 0.6, P = 0.66) after the routine care, when compared to their baseline scores. There were statistical between-group differences in GAD-7 (MD = 2.9, 95% CI = 2.2, 3.6, P < 0.001）and in the PHQ-9 scores (MD = 3.6, 95% CI = 2.9, 4.4, P < 0.001) at the post-treatment. Compared with the control group, patients had significantly lower scores on the JSS (MD = 2.7, 95% CI = 2.0, 3.3, P < 0.001), and higher scores on the PHCS (MD = −5.0, 95% CI = −6.1, −3.9, P < 0.001) after receiving Qigong and the music therapy. Conclusion: Traditional Baduanjin Qigong and five-elements music therapy help to relieve anxiety and depression, and improve the sleep quality in patients with COVID-19 infection. Trial registration: Chinese Clinical Trial Registry ChiCTR2200059800

Self-Assembling Silk-Based Nanofibers with Hierarchical Structures

Self-assembling fibrous supramolecular assemblies with sophisticated hierarchical structures at the mesoscale are of interest from both fundamental and applied engineering. In this paper, the relatively hydrophilic domains of silk fibroin (HSF) were extracted and used in studies of self-assembly. The HSF fraction spontaneously self-assembled into nanofibers, 10 to 100 μm long and 50 to 250 nm in diameter, within 2 to 8 h in aqueous conditions. Interestingly, these HSF nanofibers consisted of dozens of nanofibrils arranged in a parallel organization with assembled diameters of ∼30 nm, similar to the sophisticated hierarchical structure observed in native silk fibers. Dynamic morphology and conformation studies were carried out to determine the mechanisms underlying the HSF self-assembly process at both the nanoscale and mesoscale. The HSF self-assembled into nanofibers in a bottom-to-up manner, from “sticky” colloid particles to cylindrical globules, to form nanofibrous networks. Because of the enhanced HSF self-assembling kinetics and the hierarchical structure of HSF nanofibers, this hydrophilicity-driven approach provides further insight into silk fibroin (SF) self-assembly in vivo and also offers new tools for the recapitulation of high-performance materials for engineering applications