Chirality is ubiquitous in biology, including in biomineralization, where it is found in many hardened structures of invertebrate marine and terrestrial organisms (for example, spiralling gastropod shells). Here we show that chiral, hierarchically organized architectures for calcium carbonate (vaterite) can be controlled simply by adding chiral acidic amino acids (Asp and Glu). Chiral, vaterite toroidal suprastructure having a ‘right-handed' (counterclockwise) spiralling morphology is induced by L-enantiomers of Asp and Glu, whereas ‘left-handed' (clockwise) morphology is induced by D-enantiomers, and sequentially switching between amino-acid enantiomers causes a switch in chirality. Nanoparticle tilting after binding of chiral amino acids is proposed as a chiral growth mechanism, where a ‘mother' subunit nanoparticle spawns a slightly tilted, consequential ‘daughter' nanoparticle, which by amplification over various length scales creates oriented mineral platelets and chiral vaterite suprastructures. These findings suggest a molecular mechanism for how biomineralization-related enantiomers might exert hierarchical control to form extended chiral suprastructures.
Microfibrils are essential elements in elastic and nonelastic tissues contributing to homeostasis and growth factor regulation. Fibrillins form the core of these multicomponent assemblies. Various human genetic disorders, the fibrillinopathies, arise from mutations in fibrillins and are frequently associated with aberrant microfibril assembly. These disorders include Marfan syndrome, Weill-Marchesani syndrome, Beals syndrome, and others. Although homotypic and heterotypic fibrillin self-interactions are considered to provide critical initial steps, the detailed mechanisms for microfibril assembly are unknown. We show here that the C-terminal recombinant half of fibrillin-1 assembles into disulfidebonded multimeric globular structures with peripheral arms and a dense core. These globules are similar to the beaded structures observed in microfibrils isolated from tissues. Only these C-terminal fibrillin-1 multimers interacted strongly with the fibrillin-1 N terminus, whereas the monomers showed very little self-interaction activity. The multimers strongly inhibited microfibril formation in cell culture, providing evidence that these recombinant assemblies can also interact with endogenous fibrillin-1. The Cterminal self-interaction site was fine-mapped to the last three calcium-binding EGF domains in fibrillin-1. These results suggest a new mechanism for microfibril formation where fibrillin-1 first oligomerizes via its C terminus before the partially or fully assembled bead-like structures can further interact with other beads via the fibrillin-1 N termini. extracellular matrix ͉ fibrillinopathies ͉ Marfan syndrome ͉ protein assembly
Recent evidence indicates that a major drawback of current cartilage- and disc-tissue engineering is that human mesenchymal stem cells (MSCs) rapidly express type X collagen-a marker of chondrocyte hypertrophy associated with endochondral ossification. Some studies have attempted to use growth factors to inhibit type X collagen expression, but none to date has addressed the possible effect of the substratum on chondrocyte hypertrophy. Here, we sought to examine the growth and differentiation potential of human MSCs cultured on two polymer types, polypropylene and nylon-6, both of which have been surface-modified by glow discharge plasma treatment in ammonia gas. Cultures were performed for up to 14 days in Dulbecco's modified Eagle medium + 10% fetal bovine serum. Commercial polystyrene culture dishes were used as control. Reverse transcriptase-polymerase chain reaction was used to assess the expression of types I, II, and X collagens and aggrecan using gene-specific primers. Glyceraldehyde-3-phosphate dehydrogenase was used as a housekeeping gene. Types I and X collagens, as well as aggrecan, were found to be constitutively expressed by human MSCs on polystyrene culture dishes. Whereas both untreated and treated nylon-6 partially inhibited type X collagen expression, treated polypropylene almost completely inhibited its expression. These results indicate that plasma-treated polypropylene or nylon-6 may be a suitable surface for inducing MSCs to a disc-like phenotype for tissue engineering of intervertebral discs in which hypertrophy is suppressed.
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