Functional surface micropatterns by dewetting of thin polymer films

Patterned polymer surfaces are of great importance with respect to an increasing number of technological and bio-medical applications, due to their great versatility in terms of chemical composition, properties and processing techniques. Surface micro-patterning by spontaneous dewetting of thin polymer films represents a versatile and robust process to fabricate surfaces with controlled topography and chemistry at the micro-scale. In this Thesis, we used polymer dewetting in combination with complementary approaches to engineer both surface chemistry and the ordering of the dewetting patterns. The dewetting of poly(D,L-glycolide-co-lactide) (PLGA) thin films on polystyrene (PS) was combined with the grafting of protein-repellent poly(ethylene glycol) (PEG), in order to form topographical and chemical surface micropatterns consisting in protein-adhesive PS domains surrounded by protein-repellent PEG-grafted PLGA films. The produced micropatterned surfaces were used for site-specific protein adsorption, and represent a promising platform for biological applications, such as proteomics, single-cell studies and tissue engineering. Spatially ordered surface micropatterns were obtained by combining polymer dewetting with microcontact printing and colloidal lithography, respectively. The dewetting of thin PS films was guided within specific regions of the substrate by prestamping of the silicon substrate with self-assembled monolayers of an alkylsilane by microcontact printing. Ordered micropatterns consisting in arrays of holes with tunable size were obtained by exploiting the spontaneous dewetting of poly(4-vinyl pyridine) (P4VP) thin films on PS from the holes produced by colloidal imprinting with two-dimensional colloidal crystals assembled on the polymer bilayer

Genetic hearing loss. Some clinical and genetic aspects of the BOR syndrome, DFNA9, DFNA20/26 and DFNB1.

Contains fulltext : mmubn000001_413028933.pdf (publisher's version ) (Open Access)KUN, 14 april 2004Promotor : Cremers, C.W.R.J. Co-promotores : Huygen, P.L.M., Kremer, J.M.J.195 p

[From gene to disease: deafness and connexin 26]

Item does not contain fulltextDeafness is genetically heterogeneous, yet it is estimated that approximately half of the heritable cases of autosomal recessive deafness are caused by mutations in the gene coding for connexin 26. Connexin 26 is thought to have an essential role in the transport of potassium ions back to the endolymph of the inner ear after sound stimulation

Cross-sectional analysis of hearing threshold in relation to age in a large family with cochleovestibular impairment thoroughly genotyped for DFNA9/COCH.

Hearing threshold was analyzed for each frequency in relation to age in 88 members of a large Dutch family with cochleovestibular impairment caused by a P51S mutation in the COCH gene within the DFNA9 locus (chromosome 14q12-13). The participants in this study were 34 mutation carriers and 54 relatives without the mutation (control subjects). A sigmoidal dose-response curve with a variable slope was used to fit the mutation carriers' threshold-on-age data. Progression started at about 40 years of age and only lasted for some 20 to 25 years; the associated average progression was 2.9 dB/y for all frequencies. However, some hearing impairment was already present before, predominantly at the high frequencies. The mean thresholds in the young mutation carriers (< 33 years of age) were significantly higher (by 4 to 13 dB) than those in age-matched controls at 2 to 8 kHz. Presumably, mutation carriers have a congenital, stable offset threshold (10 to 29 dB) at these frequencies, and develop progression later in life

DFNA9/COCH and its phenotype.

Item does not contain fulltex

Inner ear anomalies are frequent but nonobligatory features of the branchio-oto-renal syndrome.

OBJECTIVE: To summarize the syndromic features and evaluate the presence of inner ear anomalies in 35 patients with branchio-oto-renal (BOR) syndrome from 6 families. DESIGN: Retrospective evaluation of magnetic resonance imaging of the temporal bones and clinical features in patients with BOR syndrome. SETTING: Tertiary referral center. PATIENTS: The study population comprised 35 clinically affected patients with BOR syndrome from 6 families. Most of these families were followed for over 25 years. MAIN OUTCOME MEASURES: Twenty-four patients underwent high-resolution, heavily T2-weighted 3-dimensional magnetic resonance imaging of the temporal bones for evaluation of inner ear anomalies. Special attention was paid to the endolymphatic duct and sac. RESULTS: A total of 7 enlarged endolymphatic ducts and sacs (3 bilaterally and 4 unilaterally) and 5 enlarged endolymphatic ducts only (2 bilaterally and 3 unilaterally) were observed. Eight hypoplastic cochleas and 6 hypoplastic labyrinths were seen bilaterally. Seven family members had normal inner ears. CONCLUSION: These findings suggest that inner ear anomalies are frequent but nonobligatory features of BOR syndrome

Contact dependent cellular interactions

The aim of this study was to investigate the contact dependent cellular interactions of neoplastic cells and somatic cells in vitro. These interactions were examined as homotypic and heterotypic interactions with focus on plasma membrane exchange and complete cell fusion of two cells. Plasma membrane exchange between the cancer cells and between cancer cells and primary fibroblasts was characterized in absolute and kinetic terms. It was found that primary human fibroblasts from skin and gingival origin were superior to cancer cells in terms of membrane exchange. This important finding demonstrates that membrane exchange similar to trogocytosis is not only a feature of immune and cancer cells as previously thought but has an important significance as cell-cell communication mechanism involved in tissue homeostasis. Complete cell fusion was examined by tagging the cell nucleus with a non-replicating baculovirus expressing chimeric nuclear proteins tagged with green and red fluorescent proteins. Complete cell fusion was not observed with fibroblasts and was only detected with SAOS-2 and MCF-7 cancer cells. It was shown that this resulted in complete nuclear fusion as the double positive cells were syncarions without exception. A large scale comparative profiling of the plasma membrane proteome of the two osteosarcoma cell lines: the good fuser SAOS-2 and the inferior one MG-63 was undertaken. Several proteins with possible involvement in the cell fusion process were identified. GP73 a protein strongly expressed in hepatocytes-derived syncytial giant cells and SED1/MFG-E8, a glycoprotein with role in sperm-egg fusion were found on the surface of SAOS-2 cells. Additionally, the presence of heat-shock proteins HSP-90 and HSP-70 which are molecular chaperons and interact with wide range of proteins were also detected on both SAOS-2 and MG-63 and thus identified as new bio-markers of osteosarcoma