Transplantation of in-vitro-generated organ buds is a promising approach toward regenerating functional and vascularized organs. Though it has been recently shown in the context of liver models, ...demonstrating the applicability of this approach to other systems by delineating the molecular mechanisms guiding organ bud formation is critical. Here, we demonstrate a generalized method for organ bud formation from diverse tissues by combining pluripotent stem cell-derived tissue-specific progenitors or relevant tissue samples with endothelial cells and mesenchymal stem cells (MSCs). The MSCs initiated condensation within these heterotypic cell mixtures, which was dependent upon substrate matrix stiffness. Defining optimal mechanical properties promoted formation of 3D, transplantable organ buds from tissues including kidney, pancreas, intestine, heart, lung, and brain. Transplanted pancreatic and renal buds were rapidly vascularized and self-organized into functional, tissue-specific structures. These findings provide a general platform for harnessing mechanical properties to generate vascularized, complex organ buds with broad applications for regenerative medicine.
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•Transplantable organ buds self-assemble from diverse and heterotypic cells•Mesenchyme-driven condensation on soft matrix is crucial for organ bud generation•Transplanted diverse organ buds quickly become vascularized in vivo•Vascularized organ buds generate functional tissues via in vivo self-organization
Takebe et al. report a generalized method for organ bud formation from diverse tissues, including kidney, pancreas, intestine, heart, lung, and brain, using heterotypic cell mixtures including mesenchymal stem cells to guide cell condensation. After transplantation, renal and pancreatic buds are readily vascularized and exhibit tissue-specific organization and function.
Organisms have evolved under gravitational force, and many sense the direction of gravity by means of statoliths in specialized cells. In flowering plants, starch-accumulating plastids, known as ...amyloplasts, act as statoliths to facilitate downstream gravitropism. The gravity-sensing mechanism has long been considered a mechanosensing process by which amyloplasts transmit forces to intracellular structures, but the molecular mechanism underlying this has not been elucidated. We show here that LAZY1-LIKE (LZY) family proteins involved in statocyte gravity signaling associate with amyloplasts and the proximal plasma membrane. This results in polar localization according to the direction of gravity. We propose a gravity-sensing mechanism by which LZY translocation to the plasma membrane signals the direction of gravity by transmitting information on the position of amyloplasts.
Control of organic crystal shape is crucial for various scientific and industrial fields, while it is still very challenging even with systematic optimization of environmental parameters such as ...temperature and concentration. Here we report an innovative approach for spatiotemporal control of organic crystal growth by directly modifying local crystal structures via femtosecond laser ablation. We found that a crystal face that is locally ablated only with a single laser pulse shows enhanced growth without the loss of crystal quality. The underlying mechanism can be explained by the generation of energetically favorable crystal growth mode (spiral growth mode), which is a fundamental growth mode for various organic crystals. We demonstrated that various crystal shapes can be achieved by femtosecond laser ablation. The fine-tuned, spatiotemporal cue given by femtosecond laser ablation will provide a facile means to obtain organic crystals with desired shape.
Green tea catechin and green tea extract are now recognized as non-toxic cancer preventives for humans. We first review our brief historical development of green tea cancer prevention. Based on ...exciting evidence that green tea catechin, (-)-epigallocatechin gallate (EGCG) in drinking water inhibited lung metastasis of B16 melanoma cells, we and other researchers have studied the inhibitory mechanisms of metastasis with green tea catechins using biomechanical tools, atomic force microscopy (AFM) and microfluidic optical stretcher. Specifically, determination of biophysical properties of cancer cells, low cell stiffness, and high deformability in relation to migration, along with biophysical effects, were studied by treatment with green tea catechins. The study with AFM revealed that low average values of Young's moduli, indicating low cell stiffness, are closely associated with strong potential of cell migration and metastasis for various cancer cells. It is important to note that treatments with EGCG and green tea extract elevated the average values of Young's moduli resulting in increased stiffness (large elasticity) of melanomas and various cancer cells. We discuss here the biophysical basis of multifunctions of green tea catechins and green tea extract leading to beneficial effects for cancer prevention and treatment.
Deformation behaviour during loading and unloading is studied in compression of an aluminium plate with a high ratio between the diameter and the thickness by a DLC coated die. A compressed plate ...becomes thinner during unloading after the plate is compressed to a larger reduction in thickness in loading. The plastic deformation of a compressed plate during unloading is confirmed by measuring the increase of the plate diameter during unloading. The optimum profile of a die crown approaches to the reverse shape of the elastic deflection of a flat die at the loading stroke end with increasing reduction in thickness.
We have succeeded in label-free visualization of spatiotemporal dynamics of laser-induced crystal precursors in aqueous solutions. The tracking-free evaluation of the diffusion-coefficient field for ...the observation domain with tens of micrometers on a side from microscopy movie data is realized by particle image diffusometry (PID). PID revealed the time fluctuation of coverage composition with the nonuniform space distribution of diffusion coefficients by the prenucleation clusters. Furthermore, the results indicate the existence of a loose aggregation domain of prenucleation clusters where the order of viscosity corresponds to that of honey.
We previously reported that giant crystal enantiomeric excess (CEE) can be obtained when sodium chlorate (NaClO3) chiral crystallization from a solution is induced by the excitation of localized ...surface plasmon resonance (LSPR) of a Au triangle trimer nanostructure by a circularly polarized laser. However, the role of the LSPR excitation in the giant CEE remains unclear. In this work, we showed, by finite-difference time-domain analysis of plasmonic near-field, that the magnitude of a chiral optical gradient force originating from the strong superchiral near-field at the Au trimer nanogap on a virtual NaClO3 chiral crystalline cluster is comparable to that of the electric-field gradient force in previous laser-trapping-induced crystallization from unsaturated solution. We revealed that the giant CEE resulted from a difference in the frequency of attachment of chiral crystalline clusters to crystal nuclei or in the local concentration due to chirally biased diffusion rather than enantioselective optical trapping.
Thin hydrogel films based on an ABA triblock copolymer gelator where A is pH-sensitive poly(2-(diisopropylamino)ethyl methacrylate) (PDPA) and B is biocompatible poly(2-(methacryloyloxy)ethyl ...phosphorylcholine) (PMPC) were used as a stimulus-responsive substrate that allows fine adjustment of the mechanical environment experienced by mouse myoblast cells. The hydrogel film elasticity could be reversibly modulated by a factor of 40 via careful pH adjustment without adversely affecting cell viability. Myoblast cells exhibited pronounced stress fiber formation and flattening on increasing the hydrogel elasticity. As a new tool to evaluate the strength of cell adhesion, we combined a picosecond laser with an inverted microscope and utilized the strong shock wave created by the laser pulse to determine the critical pressure required for cell detachment. Furthermore, we demonstrate that an abrupt jump in the hydrogel elasticity can be utilized to monitor how cells adapt their morphology to changes in their mechanical environment.
Bio-orthogonal ligations that crosslink living cells with a substrate or other cells require high stability and rapid kinetics to maintain the nature of target cells. In this study, we report ...water-soluble cyclooctadiyne (WS-CODY) derivatives that undergo an ion-pair enhanced double-click reaction. The cationic side chain of WS-CODY accelerated the kinetics on the azide-modified cell surface due to proximity effect. Cationic WS-CODY was able to crosslink azide-modified, poorly adherent human lung cancer PC-9 cells not only to azide-grafted glass substrates but also to other cells within 5–30 min. We discovered that cell–substrate crosslinking induced the ITGA5 gene expression, whereas cell–cell crosslinking induced the CTNNA1 gene, according to the adhesion partner. Ion-pair-enhanced WS-CODY can be applied to a wide range of cells with established azide modifications and is expected to provide a powerful tool to regulate cell–substrate and cell–cell interactions.
Control of crystal shape is an indispensable step for various applications of crystalline products. However, obtaining the desired crystal shape by conventionally tuning environmental conditions ...(temperature, additives, etc.) cannot always be reached. Recently, we have developed an innovative approach for spatiotemporal control of crystal growth of proteins and amino acids by locally modifying crystal structure (e.g., formation of screw dislocations) via femtosecond (fs) laser ablation. In this work, to clarify the appropriate laser condition for controlling the shape of single crystals with minimized damage, we first systematically investigated the dependence of pulse duration on laser ablation and crystal growth of l-phenylalanine (l-Phe). By using a laser system with tunable pulse durations from fs to nanoseconds (ns), we found fs laser ablation can offer nanometer-sized, sharp etching of which diameter was smaller than the diffraction limit. By utilizing such nanoprocessing via fs laser ablation for promoting the growth of a targeted crystal face, we successfully demonstrated the preparation of a bulky crystal of l-Phe, which is difficult to be obtained by conventional crystallization methods.
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