Heptatic liquid quasi-crystals by colloidal lithographic pre-assembly.

HYPOTHESIS: We hypothesize that pre-assembled lithographic Brownian seven-fold quasi-crystals (QCs) of colloidal tiles at high densities can exhibit a heptatic liquid quasi-crystal (LQC) phase upon release; such heptatic LQCs can undergo heterogeneous dynamics at different length scales, reflecting the underlying symmetry, corrugation, and hierarchy of local sets of tiles. EXPERIMENTS: We design, fabricate, and release a seven-fold QC composed of three differently shaped rhombic tiles using the method of lithographically pre-assembled monolayers (litho-PAMs). High resolution optical microscopy enables spatio-temporal particle tracking of Brownian fluctuations of many tiles in a large area over a long time. We develop an edge-proximity tessellation method for analyzing nearest neighboring particles that can be applied to assemblies and dense systems of complex shapes. FINDINGS: A fluctuating heptatic LQC phase is identified at high tile area fractions. Heterogenous dynamics and order at different length scales indicate diverse, hierarchical motif structures. We show that certain motifs can collectively rotate without any cage breaking, leading to alterations of the local tile-structure reminiscent of phason-flips in atomic QCs; this rotation causes a slow decline in the system's spatial order. We anticipate that edge-proximity tessellation will help elucidate phase transitions of other systems made of diverse building blocks having significant geometrical complexity at multiple length scales.

Hypoxia Affects Mitochondrial Stress and Facilitates Tumor Metastasis of Colorectal Cancer Through Slug SUMOylation.

BACKGROUND: Colorectal cancer (CRC) is a malignant tumor. Slug has been found to display a key role in diversified cancers, but its relevant regulatory mechanisms in CRC development are not fully explored. OBJECTIVE: Hence, exploring the function and regulatory mechanisms of Slug is critical for the treatment of CRC. METHODS: Protein expressions of Slug, N-cadherin, E-cadherin, Snail, HIF-1α, SUMO1, Drp1, Opa1, Mfn1/2, PGC-1α, NRF1, and TFAM were measured through western blot. To evaluate the protein expression of Slug and SUMO-1, an immunofluorescence assay was used. Cell migration ability was tested through transwell assay. The SUMOylation of Slug was examined through CO-IP assay. RESULTS: Slug displayed higher expression and facilitated tumor metastasis in CRC. In addition, hypoxia treatment was discovered to upregulate HIF-1α, Slug, and SUMO-1 levels, as well as induce Slug SUMOylation. Slug SUMOylation markedly affected mitochondrial biosynthesis, fusion, and mitogen-related protein expression levels to trigger mitochondrial stress. Additionally, the induced mitochondrial stress by hypoxia could be rescued by Slug inhibition and TAK-981 treatment. CONCLUSION: Our study expounded that hypoxia affects mitochondrial stress and facilitates tumor metastasis of CRC through Slug SUMOylation.

Brownian lithographic polymers of steric lock-and-key colloidal linkages.

We design and lithographically fabricate two-dimensional preassembled colloidal linkages of custom-shaped, discrete, mobile microscale tiles that are sterically coupled together by lock-and-key sub-tile features, yielding hinge-like bonds between separate tiles. These mobile colloidal linkages, which we call polylithomers, provide top-down, preconfigured, morphologically controllable analogs of fluctuating molecular polymers. We illustrate the versatility of this approach by fabricating and studying curvilinear, branched, bridged-spiral, dendritic, and mesh-like polylithomers having controllable preassembled dimensions, topologies, configurations, intrinsic local curvatures, persistence lengths, and bond extensibilities. By advancing anisotropic particle tracking routines to handle lock-and-key tiles, we measure the dynamic conformational changes of polylithomers caused by Brownian excitations to the monomer scale, revealing markedly large bond extensibilities. Beyond modeling fluctuating semiflexible molecular polymers, polylithomers provide access to unusual polymer morphologies and bonding potentials that have not yet been synthesized through other kinds of assembly methods using either molecular or colloidal monomers.

Multi-Functional Peptide-MicroRNA Nanocomplex for Targeted MicroRNA Delivery and Function Imaging.

Targeted delivery of microRNA (miRNA) mimics into specific cells/tissues and real-time monitoring on the biological function of delivered miRNA mimics at molecular level represent two major challenges in the development of miRNA-based therapeutics. Here we report a highly efficient method to address these two challenges simultaneously by using the self-assembled nanocomplex formed by miRNA mimics with a multi-functional peptide conjugate. Using the nanocomplex formed by tumor-suppressive miR-34a and the multi-functional peptide conjugate FA-R9-FPcas3 , we demonstrated the highly efficient and target-selective delivery of miR-34a into HeLa cells and tumors. With the activatable fluorescence probe integrated in the peptide conjugate FA-R9-FPcas3 , the intracellular function of miR-34a delivered by the nanocomplex to upregulate active Caspase-3 was imaged in real-time. The nanocomplex also showed significant therapeutic effects to induce apoptosis in HeLa cells and to suppress tumor growth upon tail vein injection into living mice bearing subcutaneous HeLa tumors.