Multi-domain short peptide molecules for in situ synthesis and biofunctionalization of gold nanoparticles for integrin-targeted cell uptake.

We describe design and synthesis model of multidomain (modular) peptides (MDPs), which direct a reaction cascade coupling the synthesis and surface functionalization of gold nanoparticles (AuNPs) in a single step. The synthesis is achieved via simple mixing of the aqueous solutions of auric acid and MDPs at room temperature without the addition of any surfactants or toxic intermediate reagents. This method allows facile control over the nanoparticle size between ∼2-15 nm, which opens a practical window for biomedical applications. In contrast to the conventional citrate-mediated methods, peptide-mediated synthesis and stabilization provide increased colloidal stability to AuNPs. As a proof of this concept, we demonstrate active targeting of human breast adenocarcinoma cell line (MCF7) using the one-step-prepared engineered AuNPs. Overall, we propose a single-step, chemically greener, biologically safer method for the synthesis and surface functionalization of gold nanoparticles in a size-controlled manner. The chemical versatility of the MDP design broadens the applicability of this strategy, thereby emerging as a successful alternative for the currently available nanoparticle preparation technologies.

Homozygous loss-of-function mutations in SOHLH1 in patients with nonsyndromic hypergonadotropic hypogonadism.

CONTEXT: Hypergonadotropic hypogonadism presents in females with delayed or arrested puberty, primary or secondary amenorrhea due to gonadal dysfunction, and is further characterized by elevated gonadotropins and low sex steroids. Chromosomal aberrations and various specific gene defects can lead to hypergonadotropic hypogonadism. Responsible genes include those with roles in gonadal development or maintenance, sex steroid synthesis, or end-organ resistance to gonadotropins. Identification of novel causative genes in this disorder will contribute to our understanding of the regulation of human reproductive function. OBJECTIVES: The aim of this study was to identify and report the gene responsible for autosomal-recessive hypergonadotropic hypogonadism in two unrelated families. DESIGN AND PARTICIPANTS: Clinical evaluation and whole-exome sequencing were performed in two pairs of sisters with nonsyndromic hypergonadotropic hypogonadism from two unrelated families. RESULTS: Exome sequencing analysis revealed two different truncating mutations in the same gene: SOHLH1 c.705delT (p.Pro235fs*4) and SOHLH1 c.27C>G (p.Tyr9stop). Both mutations were unique to the families and segregation was consistent with Mendelian expectations for an autosomal-recessive mode of inheritance. CONCLUSIONS: Sohlh1 was known from previous mouse studies to be a transcriptional regulator that functions in the maintenance and survival of primordial ovarian follicles, but loss-of-function mutations in human females have not been reported. Our results provide evidence that homozygous-truncating mutations in SOHLH1 cause female nonsyndromic hypergonadotropic hypogonadism.

Osteoselection supported by phase separated polymer blend films.

The instability of implants after placement inside the body is one of the main obstacles to clinically succeed in periodontal and orthopedic applications. Adherence of fibroblasts instead of osteoblasts to implant surfaces usually results in formation of scar tissue and loss of the implant. Thus, selective bioadhesivity of osteoblasts is a desired characteristic for implant materials. In this study, we developed osteoselective and biofriendly polymeric thin films fabricated with a simple phase separation method using either homopolymers or various blends of homopolymers and copolymers. As adhesive and proliferative features of cells are highly dependent on the physicochemical properties of the surfaces, substrates with distinct chemical heterogeneity, wettability, and surface topography were developed and assessed for their osteoselective characteristics. Surface characterizations of the fabricated polymer thin films were performed with optical microscopy and SEM, their wettabilities were determined by contact angle measurements, and their surface roughness was measured by profilometry. Long-term adhesion behaviors of cells to polymer thin films were determined by F-actin staining of Saos-2 osteoblasts, and human gingival fibroblasts, HGFs, and their morphologies were observed by SEM imaging. The biocompatibility of the surfaces was also examined through cell viability assay. Our results showed that heterogeneous polypropylene polyethylene/polystyrene surfaces can govern Saos-2 and HGF attachment and organization. Selective adhesion of Saos-2 osteoblasts and inhibited adhesion of HGF cells were achieved on micro-structured and hydrophobic surfaces. This work paves the way for better control of cellular behaviors for adjustment of cell material interactions.

Selective adsorption of L1210 leukemia cells/human leukocytes on micropatterned surfaces prepared from polystyrene/polypropylene-polyethylene blends.

The objective of this study is to prepare polymeric surfaces which will adsorb L1210 leukemia cells selectively more than that of healthy human leukocytes in order to develop new treatment options for people with leukemia. Chemically heterogeneous and micropatterned surfaces were formed on round glass slides by dip coating with accompanying phase-separation process where only commercial polymers were used. Surface properties were determined by using optical microscopy, 3D profilometry, SEM and measuring contact angles. Polymer, solvent/nonsolvent types, blend composition and temperature were found to be effective in controlling the dimensions of surface microislands. MTT tests were applied for cell viability performance of these surfaces. Polystyrene/polyethylene-polypropylene blend surfaces were found to show considerable positive selectivity to L1210 leukemia cells where L1210/healthy leukocytes adsorption ratio approached to 9-fold in vitro. Effects of wettability, surface free energy, microisland size geometry on the adsorption performances of L1210/leukocytes pairs are discussed.