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Abstract: Aim: The goal of this study was to understand whether dense fibrillar collagen matrices, with a hierarchical structure resembling native collagen matrices, could be useful to study collagen receptor function, in a more physiological context. The receptor analysed here was integrin α11β1, already shown to be involved in cell attachment and migration on collagen-coated plastic, and also in contraction of loose fibrillar collagen hydrogels. Materials and methods: Collagen matrices prepared here corresponded to dense fibrillar hydrogels concentrated at 5mg/ml. The behaviour of α11β1 deficient fibroblasts seeded on these concentrated matrices was assessed in terms of adhesion, morphology and migration, then compared to that observed on classical hydrogels at 1mg/ml, corresponding to loose collagen matrices. Results: Short-term attachment assays showed disturbed interactions between α11β1 deficient cells and collagen matrices in a concentration-dependent manner. Long-term assays revealed reduced cell spreading of alpha 11−/− cells on the dense collagen matrices, associated with a disturbed cytoskeleton network. Moreover, anoikis was observed when alpha 11−/− cells were seeded on 5mg/ml matrices, and not on looser 1mg/ml matrices. In scratch wound in vitro assays, carried out with cells on 5mg/ml fibrillar collagen matrices, alpha 11−/− cells migrated much better than their wild-type counterparts. In contrast, no significant difference was observed between wild and knock-out cells seeded on plastic. Conclusions: The present study demonstrates the validity of in vivo-like dense fibrillar collagen matrices to evaluate cell receptor functions more significantly than with 2D cell cultures or loose hydrogels. [Copyright &y& Elsevier]

Microtubules are key cytoskeletal components in the cytoplasm of eukaryotic cells where they have pleiotropic and vital roles in functions such as cell division, trafficking or morphogenesis. Microtubules are especially abundant in neurons. Although microtubules are in many cells dynamic polymers, they exhibit an extreme state of stability in neurons. Previous work has indicated a central role of microtubule associated proteins called STOPs in neuronal microtubule stabilization. We have recently developed STOP null mice. These mice were devoid of stable brain microtubules but to our surprise had nevertheless an apparently normal brain anatomy. However the mice showed synaptic defects affecting different forms of long- and short-term synaptic plasticity. These synaptic defects were associated with severe behavioral defects that showed a remarkable sensitivity to long-term treatment with neuroleptics. We discuss the relationship of the phenotypes observed in STOP null mice with current models of schizophrenia in which the multiple, severe, and neuroleptic sensitive mental disorders caused by the disease are due to a “disease of the synapse”. [Copyright &y& Elsevier]