Direct Surface Modification of Polycaprolactone-Based Shape Memory Materials to Introduce Positive Charge Aiming to Enhance Cell Affinity

In this study, the introduction of a positive charge on the surface of a shape memory material was investigated to enhance cell affinity. To achieve this, the direct chemical modification of a material surface was proposed. Sheet-type, crosslinked poly(caprolactone-co-α-bromo-ɤ-butyrolactone) (poly(CL-co-BrBL)) were prepared, and the direct reaction of amino compounds with bromo groups was conducted on the material surface with a positive charge. Branched poly(CL-co-BrBL) was prepared, followed by the introduction of methacryloyl groups to each chain end. Using the branched macromonomers, stable and sheet-type materials were derived through UV-light irradiation. Then, the materials were soaked in an amino compound solution to react with the bromo groups under various conditions. Differential scanning calorimetry and surface analysis of the modified materials indicated that 10 vol% of N, N-dimethylethylenediamine in n-hexane and 1 h soaking time were optimal to maintain the inherent thermal properties. The achievement of increased luminance and a positive zeta potential proved that the direct modification method effectively introduced the positive charge only on the surface, thereby enhancing cell affinity.

COUP-TFI specifies the medial entorhinal cortex identity and induces differential cell adhesion to determine the integrity of its boundary with neocortex

Development of cortical regions with precise, sharp, and regular boundaries is essential for physiological function. However, little is known of the mechanisms ensuring these features. Here, we show that determination of the boundary between neocortex and medial entorhinal cortex (MEC), two abutting cortical regions generated from the same progenitor lineage, relies on COUP-TFI (chicken ovalbumin upstream promoter–transcription factor I), a patterning transcription factor with graded expression in cortical progenitors. In contrast with the classical paradigm, we found that increased COUP-TFI expression expands MEC, creating protrusions and disconnected ectopic tissue. We further developed a mathematical model that predicts that neuronal specification and differential cell affinity contribute to the emergence of an instability region and boundary sharpness. Correspondingly, we demonstrated that high expression of COUP-TFI induces MEC cell fate and protocadherin 19 expression. Thus, we conclude that a sharp boundary requires a subtle interplay between patterning transcription factors and differential cell affinity.

Virus-like particles are good nanocarriers for liquid biopsy probes, imaging contrast agents, and anticancer medications

Recent advances in nanotechnology, chemistry, and material science have spurred the development and deployment of virus-mimetic particles. Virus-like particles have several competitive advantages. Virus-like particles are good nanocarriers for liquid biopsy probes, imaging contrast agents, and anticancer medications because of these advantages. Despite these encouraging improvements, virus-mimetic particles still have a number of shortcomings, particularly in vivo immune response and tumor targeting efficiency. The immunogenicity of virus-like particles is reduced to some extent by PEGylation of the viral capsid surface, allowing for passive tumor targeting. PEGylation, on the other hand, causes the ABC phenomenon, which results in the formation of new immune responses. Researchers are currently looking for novel materials with immune camouflage properties to negate the immunostimulatory potential of particles. Although it is projected that altering some types of virus-like particles will increase their targeted internalization, the plasma proteins adsorbed by the particles will diminish particle-target cell affinity. The corona-mediated delivery technique improves in vivo targeting effectiveness and may pave the way for clinical translation of virus-mimetic particles. With quick knowledge renewal of nanoparticle in vivo behaviors and ongoing invention of research methodologies and procedures, virusmimetic nanoparticles are projected to be completely endowed with the twin roles of immune camouflage and tumor targeting, displaying great therapeutic effectiveness.

Activated Fc receptor supramolecular complex

Phagocytosis is a part of immune response. IgG opsonized particles of greater than 1 um are recognized by Fcy receptors on the surface of professional phagocytes such as macrophages and neutrphils. IgGs are part of the immune system and is a cognate ligand of the Fc receptor. Live Cell Affinity Receptor chromatography (LARC) was used to capture an activated Fcy receptor supramolecular complex from the surface of live human neutrophils, by allowing IgG opsonized microbeads to bind to the cell surface. The cells were burst in PBS, collected and digested along side with controls. Isolated FcyR complex was analysed by LC-MS/MS. Fc and control experiment lists of SEQUEST correlated proteins were screened for a total cumulative score of at least 2400 and a minimum of three different peptides. This served as the basis of protein involvement in the FcyR mediated phagocytosis, which were then searched with iHOP for their interaction partners. Gathered interactions were then exported and Cytoscape, Osprey and String algorithms were used to generate network of interacting proteins. PAKs2-4 and PAK6 were detected with LARC. PAK2 and PAK4 were predicted by algorithms to have a central role in particle uptake. From Western Blotting, endogenous PAKs2-4 and PAK6 were detected in murine macrophages. Immunofluorescent staining was then used to verify the presence of these proteins in the forming phagosome and showed localization of PAKs to the phagosome. The same effect was observed with transfection of GFP constructs of PAKs. Upon transfection with dominant negative PAKs reduction in phagocytosis was observed.